4/5/2018. Update on Sepsis NIKHIL JAGAN PULMONARY AND CRITICAL CARE CREIGHTON UNIVERSITY. I have no financial disclosures

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1 Update on Sepsis NIKHIL JAGAN PULMONARY AND CRITICAL CARE CREIGHTON UNIVERSITY I have no financial disclosures 1

2 Objectives Why do we care about sepsis Understanding the core measures by Centers for Medicare & Medicaid services Discuss the updates pertaining to Sepsis Case 1 of year old male 24 hours of fever, productive cough, Shortness of breath and confusion Heart rate -162/min Respiratory rate - 40/min Oxygen Saturation - 90% on 15L Blood Pressure - 85/50 mmhg, MAP-61mmHg Temperature F 2

3 Why do we care about sepsis? 6 th most common inpatient diagnosis in the U.S in % are diagnosed in the ED 35% diagnosed in the wards 13% diagnosed in the ICU Mortality is 8 times higher when compared to patients admitted with other conditions Under recognized and under treated Early recognition and treatment will decrease mortality Center for Medicare and Medicaid Services (CMS) began requiring hospitals to collect data To facilitate the efficient, effective, and timely delivery of high quality sepsis care Providing timely, patient centered care, making sepsis care more affordable Reducing the use of resources and lower rates of complications 3

4 Real world financial impact The many faces of sepsis 4

5 The many faces of Sepsis Sep (1) SIRS due to infection Sep (2) 2003 SIRS due to infection (presumed or confirmed) Severe Sepsis Sepsis + acute organ dysfunction Surviving sepsis campaign and sepsis bundles use this criteria Sep (3) SIRS criteria has inadequate specificity and sensitivity New definition 5

6 What is Sepsis? CMS definition (SEP-1) 2 SIRS criteria + suspected infection Temp >101, < 96.8 HR > 90 bpm RR > 20, PaCO2 < 32 WBC > 12,000, < 4,000 or 10% bands What is sepsis? (Sep-1) Severe Sepsis Sepsis + Lactate >2 or organ dysfunction SBP < 90 MAP < 70 SBP < 40 from known baseline Cr >2 UOP <0.5ml/kg/hr for > 2 hours Bilirubin >2 Platelets < 100,000 INR >1.5 6

7 What is sepsis? (Sep-2) Septic Shock Hypo perfusion despite adequate fluid resuscitation or lactate >4 Sepsis, the many faced entity 7

8 What is sepsis? ( Sepsis-3) Organ dysfunction Increase in Sequential Organ Failure Assessment ( SOFA ) score of > 2pts SOFA Predicts ICU mortality & should be calculated upon admission Septic Shock Circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality Pressor requirement for MAP > 65 & serum lactate > 2 in absence of hypovolemia Severe sepsis is redundant Quick SOFA = qsofa Identifies high-risk patients for in-hospital mortality with suspected infection Ideal for patients outside of ICU, such as the ER or floors A score of greater than 2 suggests a high risk for poor outcome with suspected infection A positive score should make you stop and think Patients should be assessed for evidence of end organ dysfunction Can be easily repeated with any changes in patient s clinical status 8

9 qsofa Altered Mental Status Respiratory rate > 22 SBP <100 One point for each category >2 = High risk Assess for evidence of organ dysfunction Raith et al JAMA SOFA score 9

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11 Vasopressors 3 fundamental concepts One drug, many receptors acts on more than one receptor, thus multiple effects Dose response curve administered drugs are dose dependent Direct vs reflex actions 11

12 Mean arterial pressure (MAP) A multicenter, open-label trial, randomly assigned 776 patients with septic shock to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group). The primary end point was mortality at day 28. No mortality difference between groups at 28 or 90 days Increased newly diagnosed atrial fibrillation in higher MAP group Asfar et al N Engl J Med 2014 Norepinephrine (Levophed) is favored as the first-line vasopressor for septic shock in the Surviving Sepsis Guidelines (Grade 1B). Norepinephrine increases mean arterial pressure primarily through vasoconstriction, with little effect on heart rate, stroke volume, and cardiac output Dopamine increases MAP primarily through an increase in cardiac output (by increasing both heart rate and stroke volume). These characteristics make dopamine more likely than norepinephrine to cause potentially harmful tachyarrhythmias. 12

13 Vasopressin at 0.03 units/minute is appropriate to use with norephinephrine, either to improve perfusion (increase MAP) or to reduce the required dose of norepinephrine (ungraded recommendation). Vasopressin is not recommended for use as a single vasopressor for septic shock Epinephrine is considered the next-line agent for septic shock after norepinephrine in the Surviving Sepsis Guidelines. Dopamine is suggested to not be used as an alternative to norepinephrine in septic shock, except in highly selected patients such as those with inappropriately low heart rates (absolute or relative bradycardia) who are at low risk for tachyarrhythmias (Grade 2C). Phenylephrine is recommended to not be used for septic shock, except when septic shock persists despite the use of 2 or more inotrope/vasopressor agents along with low-dose vasopressin; cardiac output is known to be high, or norepinephrine is considered to have already caused serious arrhythmias (Grade 1C). 13

14 Dobutamine should be tried for patients in septic shock who have low cardiac output with high filling pressures while on vasopressors, or who have persistent evidence of hypoperfusion after attaining an adequate mean arterial pressure and intravascular volume (with or without vasopressors) (Grade 1C). What about refractory shock? Steroids Augments alpha responsiveness Reduction of inflammation from vasodilatation Helps in patients who develop adrenal insufficiency Dosing varies 200mg daily 100mg every 8 hours 50mg every 6 hours 14

15 Multicenter, double-blind, randomized trial evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. Annane et al N Engl J Med 2018 Randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the ICU, whichever came first. The primary outcome was death from any cause at 90 days. Patients who had been assigned to receive hydrocortisone had faster resolution of shock,shorter duration of the initial episode of mechanical ventilation but did not result in lower 90-day mortality than placebo. Venkatesh et al N Engl J Med

16 ATHOS -3 Trial Randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors Khanna et al N Engl J Med 2017 Manufactured by La Jolla pharmaceuticals, it is the first synthetic human angiotensin II product Approved by the FDA on December 21, 2017 for use in patients with distributive shock, predominantly septic shock. Given increased risk of DVT, the FDA recommends DVT prophylaxis while on Giapreza. At present, place in therapy is likely as a third line pressor. Cost considerations are unclear; its manufacturer is anticipating $500 million in U.S. sales. 16

17 Retrospective before-after clinical study, which compared the outcome and clinical course of consecutive septic patients treated with intravenous vitamin C, hydrocortisone, and thiamine during a 7- month period (treatment group) with a control group treated during the preceding 7 months. The primary outcome was hospital survival. Early use of intravenous vitamin C, together with corticosteroids and thiamine, was effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. Marik et al CHEST 2017 Marik Protocol Intravenous vitamin C (1.5 g every 6 hours for 4 days or until ICU discharge) IV hydrocortisone (50 mg every 6 h for 7 days or until ICU discharge followed by a taper over 3 days) IV thiamine (200 mg every 12 h for 4 days or until ICU discharge) Marik et al CHEST

18 Hydroxocobalamin Vitamin B12 precursor Nitric oxide scavenger which reverses nitric oxide mediated vasodilatation Used in cyanide toxicity Stays in bloodstream and can interfere with the Hemodialysis machine 18

19 Questions? 19