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morbidity and mortality conference. ❀ Antonio Chua, M.D. ❀ Anne Marie Kathryn Ingente, M.D. ❀ Marizen Lim, M.d. Objectives. To present a case of an acute systemic infection that caused severe sepsis and disseminated intravascular coagulation in an immunocompetent patient
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morbidity and mortalityconference ❀Antonio Chua, M.D. ❀Anne Marie Kathryn Ingente, M.D. ❀Marizen Lim, M.d.
Objectives • To present a case of an acute systemic infection that caused severe sepsis and disseminated intravascular coagulation in an immunocompetent patient • to present a case report of severe sepsis caused by a microorganism known only so far to cause disease in avian and bovine species • to briefly discuss on the recent guidelines on the management of sepsis
Identifying Data • CC • 69 y.o. /Female • married • Roman Catholic • Pasay City • Chief Complaint: • Fever and chills of few hours duration
History of Present Illness • ~12 hours PTA • tmax 37.8C, (+) chills, (+) back pain & difficulty walking; (-) urinary symptoms, (-) abdominal pain/diarrhea; (-) cough/colds/sore throat; (-) rashes/signs of bleeding • 2 hours PTA • 1x Vomiting • Consult with AMD (CBC, U/A) • Ad
History of Present Illness • CBC • Urinalysis: NORMAL (rbc: 5.5, wbc 0, epith. cells 0, bacteria 13.62) • ADMISSION
past medical history • HPN, on Metoprolol 50mg OD • Osteoporosis • abdominal surgery(?) • Family History • Unremarkable • Personal & Social History • non smoker/non alcoholic beverage drinker • hx of travel to tagaytay (2 wks PTA) • Works in a Wet Market (butcher/ sells beef products)
physical examination • General Survey: conscious, coherent, not in cardiorespiratory distress • VS: BP 90/60 HR: 102/min RR 20/min Temp 38.6C • HEENT: anicteric sclerae, pink palpebral conjunctivae, supple neck, no tonsillopharyngeal wall congestion • Skin: no pallor, no jaundice, no rashes
physical examination • CVS: adynamic precordium, tachycardic, regular rhythm, distinct heart sounds, no murmurs • Lungs: symmetrical chest expansion, clear breath sounds • Abdomen: Flabby, (+) infraumbilical scar, NABS, soft, non tender, no organomegaly • Extremities: no pedal edema, full and equal pulses
Neurologic examination • Oriented to 3 spheres • CN intact • No cerebellar deficits • Motor 5/5 on all extremities • No sensory deficits • No neck rigidity • negative brudzinky and kernig’s sign
SALIENT FEATURES • 69F • (-) DM • Butcher/sells beef products • fever x few hours PTA • low platelet count • no signs of bleeding/rashes • no urinary/respiratory/abdominal symptoms
ADMITTING IMPRESSION • SYSTEMIC VIRAL INFECTION • R/O DENGUE FEVER • HYPERTENSION, CONTROLLED
Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis & Septic Shock: 2008 • grade system: sequential assessment of the quality of evidence • A: high • B: moderate • c: low • d: very low • strength of Recommendation: • 1: strong • 2: weak • the grade of strong & weak is of greater clinical importance than a difference in letter level of quality of evidence
COURSE IN THE WARDS • 00:00 • BP 90/60 HR 102 • RR 20 Temp 38.6 • paracetamol • IV Hydration • Esomeprazole 40 IV oD • Metoclopromide 10mg prn • 02:00 • dizziness after using the commode • BP 60 palpatory (+) fever (+)tachycardic • Fluid challenge • BP responded • O2 2lpm nasal canula • ECG: non specific ST T wave changes • Cardiology Referral • Trop I 0.06 • K 3.3 Crea 1.7 • CXR: normal • Blood CS x 2 sites
PROBLEM #1: HYPOTENSION DIFFERENTIAL DIAGNOSES • SIRS • Fever • Tachycardia • WBC count • Hypotension • (CXR, Urinalysis, Blood CS) • Acute Coronary Syndrome • no chest pain, no difficulty of breathing • ECG: NSTTWC • Troponin I: 0.06
ACUTE CORONARY SYNDROME • 2007: AHA, ACC defined Myocardial Infarction as: • Evidence of myocardial necrosis (elevated cardiac biomarkers) • Clinical setting consistent with myocardial ischemia • ECG changes • Important because not all troponin elevations are due to ACS • Other Causes of Troponin elevations • sepsis • Hypovolemia • AF • Heart failure • Renal failure • Myocarditis • Pulmonary embolism
INITIAL RESUSCITATIONS (1ST 6 HOURS) • SEPTIC SHOCK (HYPOTENSION PERSISTING AFTER INITIAL FLUID CHALLENGE OR BLOOD LACTATE LEVEL ≥4 MMOL/L) • Goals: (1C) • CVP 8-12, MAP ≥ 65 • U.O ≥ 0.5mg/kg/hr • Central venous oxygen saturation ≥ 70% or mixed venous ≥ 65% (Hct > 30, dobutamine) • Diagnosis (1C) • 2 or more cultures • Imaging studies • Antibiotic therapy (1D) • Begin w/in 1st hour • Broad spectrum • Consider combination therapy in pseudomonas infection, neutropenicpxs • 7- 10 days duration Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
INITIAL RESUSCITATIONS (1ST 6 HOURS) • Source identification and control • Fluid Therapy • Crystalloids or colloids (1B) • CVP >8mmHg (1C) • Vasopressors • Maintain MAP >65mmHg (1C) • Norepinephrine and Dopamine as 1st choice of vasopressor (1C) • Inotropes • Dobutamine may be administered in the presence of myocardial dysfunction (1C) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
PROBLEM #2: ACUTE RENAL FAILURE • 06:00 • 60 palpatory HR 112 RR 20 Temp 39C • mottled skin, petechiae on her face and arms • Dopamine • Referral ID service • piperacillin-tazobactam 2.25g IV q8 • Referral Nephrology Service • Central line inserted (initial CVP 1-2; iv hydration continued); Levophed drip • Urine Na: 68 mmol/L; urine crea: 130.3 mg% • FENa: 0.006 • 07:30 • BP 70/40 • progression of petechiae on trunks, mottled skin, gcs15, no signs of meningeal irritation • for ICU transfer • Piperacillin-Tazobactam shifted to Cefepime 1g IV q12 • Metronidazole 500mg IV q8 hours • Hydrocortisone 50mg IV q6 hours
PROBLEM #3: ADRENAL INSUFFICIENCY & SEPSIS • mech of dysfxn of HPA axis during acute illness are complex & poorly understood (prob. due to ↓ prod’n of CRH, ACTH & cortisol, & dysfxn of their receptors • Corticosteroids • Consider IV hydrocortisone for adult septic pxs when hypotension responds poorly to adequate fluids and vasopressors (2C) • ACTH stimulation test is not recommended (2B) • HYDROCORTISONE DOSE SHOULD BE ≤ 300 MG/DAY (1A) • Dexamethasone should not be given (2B) • Corticosteroids should not be given in the absence of shock (1D) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
PROBLEM #4: SKIN MANIFESTATIONS • PurpuraFulminans • Purpuric lesions • Disseminated Intravascular Coagulation • CAUSES: • Meningoccoccal infections • Streptococcal infections • Staphylococcal infections • Meningoccemia • The most common cause of purpurafulminans • meningitis • Meningitis + meningococcemia • Meningococcemia – meningitis • Non specific s/sx • Classic clinical features • Rash, meningisimus, impaired consciousness
PROBLEM #4: SKIN MANIFESTATIONS • Streptoccocal Infections • 2nd most common cause of purpurafulminans • Pharyngitis, cutaneous infections, pneumonia, meningitis, invasive infections- bacteremia • Staphylocccal Infections • Not common • Presentation is similar with meningoccemia • Staphylococcus aureus strains that produce high levels of the superantigens TTST-1, SEB, SEC
COURSE IN THE WARDS • 09:00 REPEAT BLOOD WORKS:
PROBLEM #5: COAGULOPATHY • dengue duo, malaria, leptospira: negative • fdp: >80 ug/ml • LDH: 859 U/L • PBS: normocytic, normochromic RBC; leucocytosis w/ sl. shift to L; ↓ platelets
COURSE IN THE WARDS • Hematology Referral • 8U FFP transfused • Vit. K OD
BLOOD PRODUCT ADMINISTRATION • FFP: should not be used to correct lab clotting abnormality unless (+) bleeding or (+) plan of invasive procedure/s (2D) • platelet transfusion: • if with severe sepsis & plt count <5T/mm3; • or plt count 5-10T/mm3 + significant risk of bleeding; • or goal platelet count ≥50T/mm3 if surgery or invasive procedures are contemplated (2D) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
BLOOD PRODUCT ADMINISTRATION • RBC TRANSFUSION (1b) • if hgb <7g/dl • target: 7-9 g/dl • EPO (1B): • not specific tx of anemia in severe sepsis • no effect in clinical outcome • Anti-thrombin III • should not be used (1B) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
VITAMIN K • cofactor required for the activity of coagulation factors VII, IX, X, and prothrombin, and regulatory proteins (proteins C & S), & proteins of mineralized tissue (bone Gla protein and matrix Gla protein) • depending on the cause of deficiency, it can be administered in doses of 1 to 25 mg PO, IM, SQ, or IV routes www.uptodate.com Vitamin K, gamma carboxyglutamic acid, and the function of coagulation. Bruce Furie, MD, et al
PROBLEM #6: HYPOXIA & METABOLIC ACIDOSIS • MVM 0.5 • NaHCO3 drip
BICARBONATE TX • Not recommended to improve hemodynamics or decreasing vasopressor requirements in patients w/ hypoperfusion-induced lactic acidosis with ph ≥ 7.15 (1B) • its effect for ph < 7.15 is unknown Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
LACTIC ACIDOSIS IN SEPSIS • plasma lactate conc: > 4 - 5 meq/l • due to marked tissue hypoperfusion in shock (e.g. sepsis, hypovolemia, cardiac failure) • prognosis is poor unless tissue perfusion can be readily restored www.uptodate.com Causes of Lactic Acidosis. Burton D Rose, MD, et al
COURSE IN THE WARDS • 15:30 • BP 50 palpatory • dobutamine drip • 16:00 • gasping • o2sat 90-92% MVM 50% • intubated • PULMONARY Referral (azithromycin 500 IV OD, Ipatropium Br, Acetylcysteine) • CBG monitoring q6 hrs
PROBLEM #7: ACUTE RESPIRATORY FAILURE • CXR post Intubation
mechanical ventilation of sepsis-induced ALI/ARDS • target: Vt 6ml/kg (1B) • plateau pressure: upper limit: ≤ 30 cm H2O (1C) • allow permissive hypercapnea (1C) • PEEP > 5 cm H2O is usually required to avoid lung collapse (1C) • Head elevation (1B) • NIV: if w/ mild-mod hypoxia, stable hemodynamics, able to protect/clear airways (2B) • weaning (1A) • pulm. artery catheter: NOT recommended (1A) • conservative fluid strategy if w/o evidence of hypoperfusion (1C) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
GLUCOSE CONTROL • IV insulin tx (1B) • for severe sepsis w/ hyperglycemia & admitted in the icu • use a validated protocol for insulin dose adjustments (2C) • target glucose levels: < 150 mg/dl (2C) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
Course in The Wards • 19:30 • BP 80/60, HR 160’s sinus • O2sat 96% at FIO2 80 • still with metabolic acidosis • CVP 3-4 • restless, follows commands • Referral to Anesthesiology for sedation (not done) • 1 dose of Vancomycin 1g IV
sedation, analgesia & NM blockade in sepsis • use sedation protocols in critically ill ventilated pxs to reduce duration of mech. vent. & icu stay (1B) • intermittent bolus sedation or continuous infusion sedation w/ daily interruptions (1B) • NM blocking agents: should be avoided, if possible (1B) • reduces tissue utilization of O2 thereby decreasing formation of lactic acid Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
other tests done • Glu: 71.89 mg/dL • HbA1C: 6.5% • SGOT: 142 U/L (15-37) • TB: 2.8 mg/dL(0-1) • TP: 5.2 g/dL(6.4-8.2) • alb: 2.8 g/dL (3.4-5) • UA: 6.83 mg/dL (2.6-6) • HDL: 30.5 (40-60) • LDL: 102.14 (0-100) • repeat ecg: sinus tachycardia • 2DE: IVSH w/ NLVWMC. EF 76% • abdominopelvic USG: consider liver parenchymal disease. Thick gallbladder wall, non specific in etiology. Normal biliary tree, spleen and kidneys
Course in the wards • 19:30 • Anuric: HD not done (unstable hemodynamics; coagulopathy)
Renal Replacement Therapy • continuous RRT & intermittent HD is suggested in severe sepsis and ARF (2b) • use of cont. rrt is suggested to facilitate management of fluid balance in hemodynamically unstable septic pxs (2b) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
course in the wards • 27:00 • transferred to icu • BP 60 palpatory • Epinephrine drip started • CP arrest 20 min CPR • GCS 3, BP 40 palpatory (Quadruple vasopressors) • 31:00 DNR signed
consideration for limitation of support • advance care planning including communication of likely outcomes & realistic good treatments should be discussed with patients and families (1D) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
course in the wards • 40:00 • patient expired • autopsy done
Preliminary autopsy report • Immediate cause of death: disseminated intravascular coagulation, 2° to septicemia • contributory cause of death: • hemorrhage, adrenals, lungs and pericardium • acute respiratory distress syndrome • acute bacterial meningitis • extensive tubular necrosis, bilateral kidneys
preliminary autopsy report • non contributory cause of death: • hypertrophy of the heart, predominantly left ventricle • atherosclerosis of the aorta with calcification • micro and macrosteatosis, liver
disseminated intravascular coagulation • consumption coagulopathy & defibrination syndrome • systemic process producing both thrombosis and hemorrhage • a complication of an underlying illness occurring in ~1% of hospital admissions
dic: etiology • sepsis (40%) • trauma & tissue destruction • malignancy • ob complications