FN, sepsis and shock

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  • Dopamine- Intermediate dosages from 5 to 10 μg/kg/min, known as the "cardiac dose", additionally have a positive inotropic and chronotropic effect through increased β1 receptor activation. Dopamine is used in patients with shock or heart failure to increase cardiac output and blood pressure.Dopamine begins to affect the heart at lower doses, from about 3 μg/kg/min IV.High doses from 10 to 20 μg/kg/min are the "pressor dose". This dose causes vasoconstriction, increases systemic vascular resistance, and increases blood pressure through α1 receptor activation, but can cause the vessels in the kidneys to constrict to the point that urine output is reduced.
  • FN, sepsis and shock

    1. 1.  Mild <1500/microL, moderate <1000/microL, severe <500/microL  Primarily useful for other forms of neutropenia, such as viral- induced or congenital/cyclical Neutropenia is defined as an ANC < 500/ microL in cancer patients
    2. 2. Definition: An absolute neutrophil count (ANC) < 1500/microL 7.9 segs 8% L 82% 3.7 98 Bands 2% B 3% 23 M 4% E 1% How do you calculate ANC? Total WBC count x (% neutrophils + % bands) 100
    3. 3.  Risks of infection related to ◦ Duration of neutropenia ◦ Degree of neutropenia ◦ Factors that predispose to infection  Mucosal and skin breakdown  Altered immune system  Central venous catheters
    4. 4.  In a Neutropenic Patient ◦ A single oral temperature > 38.3 C ◦ A temperature of 38C for longer than one hour, or two elevations greater than 38C in a 12 hour period How about a rectal temperature? ◦ Due to associated risks of mucosal trauma and bad- ass bacteremia, neutropenic patients should have nothing introduced per rectum  Thermometer  Digital Exam  Suppository  Enema
    5. 5.  In patients with cancer, infection is a major cause of morbidity and mortality ◦ Fever may be the first and only indication of infection in a neutropenic patient ◦ Some patients may be afebrile, but are hypothermic, hypotensive, lethargic, and/ or confused. Do not assume that if there is no fever, there is no infection! ◦ Treat empirically if there are signs of clinical deterioration in a neutropenic child, even if afebrile
    6. 6.  Bacteremia is the most common cause! ◦ Approximately 20% of patients with fever and neutropenia will have a positive blood culture
    7. 7. Infections Gram – Fungi Viral Gram + - E coli- Coag neg staph - Klebsiella - Candida - HSV- Strep viridans - Pseudomonas - Aspergill sp - VZV- Staph aureus - Acinetobacter - Cryptococ sp - Enterobacter sp
    8. 8.  GI tract flora (oral/intestinal mucositis) Diarrhea ◦ C. difficile, salmonella Upper respiratory tract Lower respiratory tract Urinary tract Skin Soft tissues
    9. 9.  Thorough history ◦ Sick contacts ◦ Review of systems – little things mean a lot Careful physical exam ◦ All skin – note even slight erythema ◦ Perirectal area (but no rectal exam) ◦ Mucosa ◦ Line sites, surgical sites, LP/BMA sites Laboratory/ imaging studies:  CBC w/ diff  Blood/ fungal cultures (from all lumens of central line)  Symptom/history/risk based: chest x-ray, NP swabs, lumbar puncture, urine cx, stool studies, wound cx
    10. 10.  infectious or non-infectious insult leading to an inflammatory cascade, vasodilation, and capillary endothelial leak, presenting with 2 or more of the following: ◦ fever >38C or <36C, ◦ HR >90 ◦ RR >20, ◦ WBC >12 or <4 or >10% bands
    11. 11.  What is shock? ◦ Inadequate oxygen delivery to meet the metabolic needs of the tissues. What shock isn’t: ◦HYPOTENSION
    12. 12.  Compensated ◦ Vital organ system is preserved Uncompensated ◦ Ability to regulate blood flow is compromised Irreversible ◦ Damage of vital end organs leading to multiple organ system failure
    13. 13.  Tachycardia Tachypnea Dry mucous membranes Flash capillary refill (“warm shock”) Prolonged capillary refill Decreased urine output Altered mentation Hypotension
    14. 14.  A late finding in pediatric patients Children may lose 40-50% of their circulating blood volume before they become hypotensive
    15. 15.  Hypovolemic Cardiogenic Septic Distributive Obstructive
    16. 16.  Causes: intravascular volume depletion ◦ Diarrhea and Dehydration ◦ Hemorrhage ◦ Operative losses
    17. 17.  Heart rate CVP Urine Output Prolonged Capillary refill Dry mucous membranes Poor skin turgor Altered mentation Hypotension
    18. 18.  CHF Congenital heart disease Dysrhythmias Infections/Myocarditis Metabolic Dilated Cardiomyopathy Connective Tissue Disorders
    19. 19.  Impediments to cardiac output ◦ Pericardial effusion/Pericardial tamponade ◦ Tension Pneumothorax ◦ Systemic hypertension ◦ Congenitally acquired outflow tract obstructions
    20. 20.  Disruption of normal vasomotor tone ◦ Anaphylaxis ◦ Spinal or Epidural analgesia ◦ “Spinal shock”–disruption of the spinal cord ◦ Sepsis
    21. 21.  Capillary leak, myocardial depression ◦ Bacteria ◦ Viruses ◦ Fungi
    22. 22.  Inflammation is the normal host response to infection ◦ It serves to localize and control bacterial invasion and to initiate repair of injured tissue Sepsis results when the inflammatory response to infection becomes generalized ◦ It extends to involve healthy tissue remote from the site of infection
    23. 23.  Sepsis is a clinical syndrome due to a systemic response to severe infection  Infection causes a release of inflammatory mediators  These cause systemic inflammation and widespread tissue injury  Maldistribution of intravascular volume and depression of myocardial function result in shock
    24. 24.  Volume 20 cc/kg x 3 of crystalloid May use colloid ◦ PRBCs if anemic ◦ 5% albumin if hypoalbuminemic ◦ Platelets if suspicion of active bleeding and thrombocytopenic If no response to 60 cc/kg, establish central monitoring and initiate inotropic support Antibiotics, antivirals, antifungals ◦ Important, but less important than fluids
    25. 25.  Airway Oxygenation Ventilation Normal perfusion Normal blood pressure Threshold heart rate Infants: 90-160 bpm Children: 70-150bpm
    26. 26.  Normal mental status Normal blood pressure for age (reliable when pulses are palpable) Normal pulses-no difference between central and peripheral pulses Capillary refill < 2 seconds
    27. 27.  Warm extremities Urine output > 1 ml/kg/h Normal glucose level Normal calcium level
    28. 28.  Pulse oximeter ECG Blood pressure monitoring Temperature Urine output Glucose Ionized Calcium
    29. 29.  In a patient with suspected septic shock, how fast should you give the initial 20ml/kg bolus? ◦A: As fast as possible!  Push is literal – you should actually be pushing on the bag or syringe of fluid. Your hand should hurt.
    30. 30.  Volume Volume Volume Volume **Average requirement 40-60 ml/kg Monitor for work of breathing, rales, gallop, hepatomegaly
    31. 31.  Dopamine ◦ First line drug ◦ Drip at 5-10 mcg/kg/min to start ◦ More beta adrenergic at low doses, alpha at high doses Epinephrine ◦ Fluid refractory, dopamine-resistant cold shock Norepinephrine ◦ Fluid refractory, dopamine-resistant warm shock ◦ More alpha adrenergic
    32. 32.  Risk for adrenal insufficiency ◦ CAH ◦ Previous steroid exposure ◦ Hypothalamic/pituitary abnormality Shock despite epinephrine or norepinephrine infusion Send a cortisol level and initiate hydrocortisone therapy at stress-level dosing
    33. 33.  Timely initiation of broad spectrum empiric parental antibiotics ◦ Considerations in antibiotic choices:  Types of bacterial isolates found in the institution  Antibiotic susceptibility patterns  Patient’s drug allergies  Organ dysfunction (i.e. renal, hepatic)  Type of chemo regimen given and last time administered (i.e. there is an association between Strep viridans infection and high dose cytarabine therapy)
    34. 34.  Good data supports the use of monotherapy with a single antipseudomonal broad- spectrum agent However, many use combination therapy for synergistic effects and possible reduction of drug resistance ◦ Combination therapy: Aminoglycoside + antipseudomonal penicillin, cefepime, ceftazidime, or a carbapenem
    35. 35.  Improves coverage of gram-positive organisms ◦ Febrile neutropenic patients are expected to defervesce after 48-72h of broad-spectrum antibiotics ◦ If the patient is still febrile after 48-72 hrs of antibiotic coverage, the next drug we add at MSKCC is Vancomycin ◦ It may be added at initiation of broad spectrum antibiotics if there is a strong suspicion of infection with a gram positive organism
    36. 36.  The efficacy of adding vancomycin at the beginning of treatment has not been proven ◦ Up to 2/3 of bacterial isolates from blood in febrile neutropenic cancer patients are gram + cocci ◦ Addition of Vancomycin at the start of treatment has not shown an impact in either morbidity or mortality  Empiric therapy is also discouraged because its use increases the probability of colonization of infection with Vancomycin-resistant enterococci (VRE)
    37. 37.  Fungal treatment is generally added when patients are persistently febrile after 5-7 days of broad spectrum antibiotics and negative blood cultures ◦ At MSKCC, we usually add Liposomal Amphotericin (AmBisome) after 5-7 days of persistent fever (Voriconazole alternative) ◦ Use of Amphotericin B therapy is limited due to substantial toxicity, particularly nephrotoxicity
    38. 38.  Additional anaerobic coverage is generally with metronidazole ◦ Indications include persistent diarrhea, positive stool cultures (clostridium difficile), areas of perianal infection (erythema, fissures, rectal pain/ possible typhlitis)
    39. 39.  Length of treatment varies by center At MSK, all antibiotics are continued until: ◦ ANC is >0.5 AND ◦ Patient is afebrile for at least 24 hours If cultures are positive, length of treatment is determined in consultation with ID ◦ This will also depend on type of infection and intervention
    40. 40.  Fever & Neutropenia is for real Treat suspected sepsis immediately ◦ Fix the fluid overload later ◦ PUSH is literal. PUSH the fluid. Choose antibiotics based on institution and patient history ◦ You can always change later

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