ASandler_Sepsis topic discussion.docx

1. 1 Infection Inflmmatory response Hyperocagulability Organ Damage Hypoperfusion and Organ Damage Endothelial dysfunction Vasodilation Platelet-fibrin clots and microthrombi Tissue factor TNF, IL-6 Lactate ANG II receptor Pathophysiology: An interplay between Inflammatory and hemostatic processes Cortisol  Life-threatening organ damage resulting from dysregulated host response to an infection  Septic shock: Sepsis+ circulatory compromise+ metabolic and cellular abnormalities o Higher mortality  ~30 million affected o ~6 million deaths annually  > $20 million healthcare cost in 2011 Sepsis and Septic Shock Anna Sandler PharmD Candidate, 2023 Background: The highest healthcare expense Vaso- pressin Vaso- pressin Other noteworthy culprits ANG: Angiotensin; TNF: Tissue necrosis factor

2. 2 qSOFA SOFA Altered mental status Low PaO2 RR ≥ 22 Hypotension SBP ≤ 100 Low platelets, high bilirubin AKI Low Glasgow Coma Scale Common Offenders Escherichia coli MSSA Streptococcus spp. S. pneumoniae MRSA Pseudomonas aeruginosa Enterobacter spp. Suspect • Fever • Elevated WBC • Positive cultures • Anion gap metabolic acidosis Screen • qSOFA or SIRS • ≥ 2 points Confirm • SOFA • ≥ 2 points baseline increase= organ dysfunction Presentation, Diagnosis, Goals of Treatment Goals of treatment Time Minimize ADRs Septic Shock MAP < 65 mmHg Infection Control Lactate > 2 mmol/L Infection Control Preserve organ function MAP: mean arterial pressure; MSSA: methicillin susceptible staphylococcus aureus; MRSA: methicillin resistant s. aureus; qSOFA: Quick Sequential Organ Failure Assessment; RR: Respiration rate; SIRS: Systemic inflammatory response syndrome; SPP: species; WBC: white blood cell count

3. 3 Pressor Receptors Effect NE α1++ β1+ Increased venous and arterial tone Epinephrine α1+++ β1+++ β2+++ Tachycardia Lactic acidosis Hyperglycemia Peripheral ischemia Vasopressin V1a Peripheral ischemia Cardiac arrhythmia Norepinephirne Vasopressin Epinephrine Therapies  Vasopressors o First-line: Norepinephrine (NE) o Inadequate MAP with NE: vasopressin Dose  NE: 0.05-0.15 mcg/kg/minute  Vasopressin: 0.01-0.04 units/minute Monitoring: Intravascular volume and organ perfusion  MAP  Arrhythmias  Splanchnic and digital ischemia Treatment: Fluid Resuscitation immediately upon suspicion of sepsis or septic shock Treatment: Hemodynamic management after fluid resuscitation Therapies  Crystalloids > colloids o 0.9% NaCl (NS) o Lactated Ringers (LR), “Balanced”  Increasing use of balanced solutions/ “chloride- restrictive” o Hyperchloremic metabolic acidosis o AKI Dose  Initial: 30 mL/kg  Subsequent: Guided by patient assessment Monitoring: Intravascular volume and organ perfusion  MAP  Fluid challenges  Capillary refill time  Extremity temperature Goal time: Within first 3 hours AKI: Acute Kidney Injury What about IV corticosteroids?  If fluids and vasopressors are insufficient to restore hemodnyamic stability o IV Hydrocortisone 200mg/day Steroids?

4. 4 MRSA coverage Other commonly used agents Pseudomonas Vancomycin Daptomycin Linezolid Ceftriaxone Cefepime Cefotaxime Cefepime Ceftazidime Meropenem Imipenem Agent Utility Recommendation/evidence ANG II Vasoconstrictive effects for hemodynamics Potential adjunctive vasopressor therapy Low quality evidence VTE prophylaxis Prevent clots LMWH > Heparin IV Vitamin C Potential anti- inflammatory properties Guidelines suggest AGAINST Bicarbonate Acidosis treatement Potentially if severe metabolic acidemia is present Additional considerations and recommendations Treatment: Anti-infectives-early administration is a very effective intervention Empiric coverage: Broad and IV  Based on guidelines for infection source  MRSA o Only those at high-risk o ONLY High-risk of MDROs  Double gram-negative coverage MRSA coverage Other commonly used agents Pseudomonas Vancomycin Daptomycin Linezolid Ceftriaxone Cefepime Cefotaxime Cefepime Ceftazidime Meropenem Imipenem  Initiate regardless of procalcitonin level  General concept: Broad and IV Empiric coverage  Based on guidelines for infection source  MRSA o Only those at high-risk o ONLY High-risk of MDROs  Double gram-negative coverage  De-escalate once causative pathogen and susceptibilities are known Pharmacokinetics  Optimizing PK/PD parameters o Prolonged beta-lactam infusions Goal times Goal times 1 hour 1 hour 3 hours 3 hours Recognition Recognition Probable sepsis +/- shock Probable sepsis +/- shock Possible sepsis + shock Possible sepsis + shock Possible sepsis - shock Possible sepsis - shock 0 hour Pharmacokinetics  Optimizing PK/PD parameters o Prolonged beta-lactam infusions Other considerations  Source control  De-escalation  Fungal coverage in those with risk factors Other considerations  Source control  De-escalation  Fungal coverage in those with risk factors MDRO: Multi-drug resistant organism Anti-fungal agents only in high-risk patients DDD: Don’t forget: Daily evaluation +De-Escalation

5. 5 Drug MOA-class/Coverage Sepsis Dosing ADRs, Monitoring, Warnings Normal Saline 30 mL/kg within first hour Hyperchloremic metabolic acidosis AKI Fluid overload Lactated Ringer’s 30 mL/kg within first hour Hyperkalemia Monitoring: K, Cl, Ca, osmolarity Calcium in LR binds to ceftriaxone CI in neonates requiring LR; flush lines between administration in older adults Norepinephrine (Levophed) α1>β1 activity Vasoconstriction with some ionotropic and chronotropic effects 5-15 mcg/min (0.05-0.15 mcg/kg/minute) Extravasation-infuse into large, central vein if possible Vasopressin (Vasostrict) Pure vasoconstrictor Stimulates V1 receptor and increases systemic vascular resistance 0.01-0.04 unites/minute Non-titrating drip Epinephrine (adrenaline) Potent α1 and β1agonist 1-15 mcg/min (0.01-0.2 mcg/kg/minute) Tachycardia Tachyarrhythmias Extravasation Increased lactate Hydrocortisone Cortisol replacement Anti-inflammatory 50 mg bolus every 6 hours or 200 mg/dayhyd Hyperglycemia Vancomycin (Vancocin) Glycopeptide antibiotic G+, MRSA, 15-20 mg/kg/dose every 8-12 hours or per hospital protocol Loading dose recommended Renally dose adjusted Monitor target trough levels ADRs: Injection site reactions, nephrotoxicity, ototoxicity, Red man syndrome Piperacillin-Tazobactam (Zosyn) Beta lactam-Beta lactamase inhibitor, G+, EB, PsA, anaerobes 4.5 g IV every 6 hours Renally dose adjusted ADRs: Diarrhea, flushing, thrombophlebitis, anaphylaxis

6. 6 Drug MOA- class/Coverage Sepsis Dosing ADRs, Monitoring, Warnings Cefepime (Maxipime) Fourth generation cephalosporin/G+, EB, PsA 2 g IV every 8 hours Renally dose adjusted ADRs: Injection site reactions, skin rash, D/N/V Ceftriaxone/Rocephin Third generation cephalosporin/ G+, EB Based on source of infection Not renally dose adjusted DO NOT use in hyperbilirubinemic neonates DO NOT coadminister with calcium-containing solutions ADRs: Injection site reaction, pruritis, skin rash, flushing, anemia, thrombocytopenia, increased LFTs Meropenem (Merrem) Carbapenem/ G+, EB, PsA. anaerobes 1-2 g IV every 8 hours Renally dose adjusted DDI with valproic acid decreased levels+ increased risk of seizures ADRs: skin rash, diarrhea, flatulence, anemia, injection site reaction, seizures, Linezolid (Zyvox) Oxazolidinone G+, MRSA, Based on source of infection Not renally dose adjusted ADRs: Thrombocytopenia, rare peripheral or optical neuropathy EB: Enterobacter; G+: Gram positive, generally includes streptococcus, methicillin-susceptible Staphylococcus aureus (MSSA) , and enterococci; note, all cephalosporins lack coverage against enterococci; PsA: Pseudomonas Aeruginosa, V1: Arginine vasopressin 1a (AVP1a) receptor

7. 7 Picture links: https://www.nidirect.gov.uk/news/recognising-signs-and-symptoms-sepsis https://www.amenclinics.com/blog/mold-affect-brain/ https://www.svhlunghealth.com.au/conditions/ards-acute-respiratory-distress-syndrome https://www.shutterstock.com/search/liver https://www.healthline.com/health/lactated-ringers https://www.uptodate.com/contents/image?imageKey=PULM%2F99963 References 1. Corrêa, T.D., Takala, J. & Jakob, S.M. Angiotensin II in septic shock. Crit Care 19, 98 (2015). https://doi.org/10.1186/s13054-015-0802-3 2. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y 3. Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Med. 2019;7:2050312119835043. doi:10.1177/2050312119835043 4. Jadhav, A. P., & Sadaka, F. G. (2019). Angiotensin II in septic shock. The American journal of emergency medicine, 37(6), 1169-1174. 5. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):762. doi:10.1001/jama.2016.0288 6. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):775. doi:10.1001/jama.2016.0289 7. Shi, R., Hamzaoui, O., De Vita, N., Monnet, X., & Teboul, J. L. (2020). Vasopressors in septic shock: which, when, and how much?. Annals of Translational Medicine, 8(12). 8. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801. doi:10.1001/jama.2016.0287 9. Torio CM, Moore BJ. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013: Statistical Brief #204. In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Agency for Healthcare Research and Quality (US); 2006. Accessed July 9, 2022. http://www.ncbi.nlm.nih.gov/books/NBK368492/

ASandler_Sepsis topic discussion.docx

ASandler_Sepsis topic discussion.docx

ASandler_Sepsis topic discussion.docx

Recomendados

Más contenido relacionado

Similar a ASandler_Sepsis topic discussion.docx

Similar a ASandler_Sepsis topic discussion.docx(20)

Más de AnnaSandler4

Más de AnnaSandler4(20)

Último

Último(20)

ASandler_Sepsis topic discussion.docx