Shock with a focus on Septic shock in pediatrics

management of Septic shock in Pediatric patients

1. Septic shock in pediatrics Presenter: Dr Alia Karimbaksh

2. Sepsis Definition Sepsis is a clinical syndrome of life- threatening organ dysfunction caused by a dysregulated response to infection Causes: Bacterial Viral Fungal

3. Staging

4. Septic Shock Septic shock is defined as persisting hypotension requiring vasopressors to maintain mean arterial pressure despite adequate volume resuscitation

5. Pathophysiology Local infection Bacteria releases toxins into blood stream Inflammatory response Increase vascular and capillary permeability Massive vasodilation & thrombosis Further inflammatory response Decrease in blood pressure Hypotension

6. Neonatal Infants/ older children Prematurity Premature or prolong ROM Meconium stained amniotic fluid Chorioamnionitis Group B streptococcal (GBS) rectovaginal colonization Urinary tract infection Age younger than one month Serious injury ( eg , major trauma, burns, or penetrating wounds) Chronic debilitating medical condition ( eg , frequent aspiration pneumonia, uncorrected congenital heart disease) Host immunosuppression (malignancy, human immunodeficiency virus infection, severe malnutrition, congenital immunodeficiency, sickle cell disease or immunomodulating medications [ eg , chemotherapy]) Large surgical incisions In-dwelling vascular catheters or other invasive devices ( eg , endotracheal tube, Foley catheter, chest tube) Urinary tract abnormalities with frequent infection Risk factors

7. Clinical Manifestation Warm Shock Cold shock Flash capillary refill (<1 second) Bounding pulses Warm, dry extremities Wide pulse pressure (typically greater than 40 mmHg in older children and adults; lower pulse pressures may reflect widening in infants and neonates Delayed capillary refill (>2 seconds) Diminished pulses Mottled or cool extremities Narrow pulse pressure (typically <40 mmHg in older children and adults)

8. Physical Findings Toxic or ill appearance Signs of dehydration ( eg , dry mucus membranes, sunken eyes, decreased urine output, prolonged capillary refill time, decreased skin turgor, and, in infants, a sunken fontanelle) Rigors Altered mental status ( eg , irritability, anxiety, confusion, lethargy, somnolence) Decreased tone in neonates and infants Seizures Respiratory depression or failure

9. Pulmonary rales or decreased breath sounds caused by bronchopneumonia Distended, tender abdomen ( eg , perforated viscus or intraabdominal abscess) Costovertebral angle tenderness ( eg , pyelonephritis) Skin cellulitis or abscess Peripheral edema caused by capillary leak Petechiae or purpura suggesting either a specific infectious source ( eg , meningococcemia, rickettsial infection)

10. Investigations CBC & blood smear: –Hb/ Hct , blood film ( Anaemia ) – Buffy-coat smear of peripheral blood: In early sepsis, abnormalities may include: Leukocytosis or leukopenia: Neutrophilia or neutropenia In viral infections lymphocytosis predominates. Thrombocytopenia may be present – Evidence of haemolysis suggests clostridial bacteremia, malaria, a drug reaction, or DIC. – Pancytopenia may indicate bone marrow involvement

11. Renal function: BUN & Serum creatinine (assess dehydration & organ failure) Liver function test: Hypoalbuminaemia likely to be present. Cholestatic jaundice with elevated levels of serum bilirubin (mostly conjugated) and alkaline phosphatase may be present.

12. Glucose: Hyperglycaemia may be present initially as a stress response. Hypoglycaemia may be present later Urine dipstick and sample for microscopy, culture and sensitivity: Proteinuria may be present Imaging Chest X-ray CT scan

13. Treatment 1.  Recognize signs of poor perfusion (0-5min) Decreased mental status Cold extremities Delayed capillary refill Weak pulses, differential central and peripheral pulses Low urine output Hypotension or low BP: Minimum systolic BP by age: < 1mo: 60 mmHg; 1mo to 10y: 70 + (2 × age in years); ≥10y: 90 mmHg 2.  Assess ABCs (0-5 min) Provide 100% oxygen at high flow rate (15L) Early intubation may be necessary in neonates and infants Breathing assistance as necessary, including mechanical ventilation

14. 3. Establish IV access and place on monitor (0-5min) 2 large-bore peripheral IVs (PIVs) preferred: if difficult IV, place IO access Consider labs on IV placement: blood gas, lactate, glucose, ionized calcium, CBC, cultures (glucose check through finger stick preferred for rapid result) 4. Fluid and electrolyte resuscitation (5-15min) Fluids: Push 20 mL/kg fluid (isotonic crystalloid) IV/IO over 5-20min or faster if needed (reassess for signs of shock) Repeat 20 mL/kg bolus push of fluid (up to 60 mL/kg) until clinical symptoms improve or patient develops respiratory distress/rales/ hepatomegaly May continue to require additional fluid above 60 mL/kg (fluid refractory) Fluid needs may approach 200 mL/kg in warm septic shock (warm extremities, flash capillary refill)

15. Correct hypoglycemia: Glucose levels in hypoglycemia: Neonates < 45 mg/dL; infants/children < 60 mg/dL Treatment options to provide 0.5-1 g/kg glucose: For infant/child: dextrose 25% in water: 2-4 mL/kg IV/IO; dextrose 10% in water: 5-10 mL/kg IV/IO; for neonate: dextrose 10% in water: 2-4 mL IV/IO; consider maintenance fluid containing dextrose Correct hypocalcemia for low ionized calcium: Calcium gluconate 100 mg/kg IV/IO (max 2g) PRN Calcium chloride 20 mg/kg IV/IO PRN

16. 5. Infection control (5-60min) General treatment recommendations : Empiric therapy should be used for unknown etiology of sepsis; Tailoring of therapy to address suspected pathogens or to achieve adequate drug penetration may be necessary; Broader initial coverage may be needed for initial stabilization

17. Neonates: Ampicillin plus  gentamicin: Ampicillin for 0-7d: 50 mg/kg IV/IM/IO q8h; ampicillin >7d: 50 mg/kg IV/IM/IO q6h plus  gentamicin (dosing institution dependent): 4mg/kg IV/IO/IM q24h (alternative for 0-7d: 2.5 mg/kg IV/IO/IM q12h; alternative for >7d: 2.5 mg/kg IV/IO/IM q8h)  or Ampicillin plus  cefotaxime: Ampicillin for 0-7d: 50 mg/kg IV/IM/IO q8h; ampicillin >7d: 50 mg/kg IV/IM/IO q6h plus cefotaxime 50 mg/kg IV/IO q8h Infants (>1mo) and children: Ceftriaxone 75 mg/kg (max 2g) IV/IO/IM q24h plus vancomycin 15mg/kg (max 1g) IV/IO q8h

18. Immunosuppressed patients: Vancomycin 15 mg/kg IV/IO (max 1 g/dose) q8h plus cefepime 50 mg/kg IV/IO (max 2g/dose) q8h; consider antifungal therapy Patients at increased risk of fungal infection ( eg , identified fungal source, immunocompromised with persistent fever on broad-spectrum antibiotics): •Add liposomal amphotericin B or an echinocandin ( eg ,  caspofungin , micafungin) to the antimicrobial regimen . If candidemia is suspected, an echinocandin is the agent of choice. Patients with risk factors for rickettsial infection ( eg , travel to or reside in an endemic region): •Add a tetracycline antibiotic ( eg , doxycycline) to the antimicrobial regimen. Duration of therapy: Determined by ultimate source of infection; 7-10d is typically sufficient Above regimens may be empiric therapy for 48-72h, until cultures and sensitivities are known, so as to accurately tailor treatment

19. 6. Fluid-refractory shock (persisting after 60 mL/kg fluid) (15-60 min) Continue fluid resuscitation and initiate vasopressor therapy titrated to correct hypotension/poor perfusion Central line placement and arterial monitoring if not already established; vasopressors should not be delayed for line placements Normotensive shock (impaired perfusion but normal blood pressure): Dopamine 2-20 mcg/kg/min IV/IO, titrate to desired effect; if continued poor perfusion, consider dobutamine infusion 2-20 mcg/kg/min IV/IO, titrate to desired effect (may cause hypotension, tachycardia) Warm shock (warm extremities, flash capillary refill): Norepinephrine 0.1-2 mcg/kg/min IV/IO infusion, titrate to desired effect Cold shock (cool extremities, delayed capillary refill): Epinephrine 0.1-1 mcg/kg/min IV/IO infusion, titrate to desired effect

20. 7. Shock persists following vasopressor initiation (60 min) Continued fluid replacement; obtain CVP measurement to guide SvO2 < 70% (cold shock): Transfuse Hgb >10 g/dL; optimize arterial saturation through oxygen therapy, ventilation; epinephrine 0.1-1 mcg/kg/min IV/IO infusion, titrate to desired effect SvO2 < 70% (normal BP but impaired perfusion): Transfuse Hgb >10 g/dL; optimize arterial saturation through oxygen therapy, ventilation; consider addition of milrinone 0.25-0.75 mcg/kg/min IV/IO (titrate to desired effect) or nitroprusside 0.3-5 mcg/kg/min IV/IO (titrate to desired effect) SvO2 >70% (warm shock): Norepinephrine 0.1-2 mcg/kg/min IV/IO infusion, titrate to desired effect; consider vasopressin 0.2-2 mU /kg/min infusion, titrate to desired effect

21. 8. Fluid refractory and vasopressor-dependent shock) (60 min) Consider adrenal insufficiency Hydrocortisone 2 mg/kg (max 100mg) IV/IO bolus; obtain baseline cortisol level; if unsure, consider ACTH stimulation test; duration depends on response, laboratory evaluation 9 . Supplemental therapies Blood transfusion considered for Hgb < 10 g/dL (ideal threshold for transfusion unknown) Sedation/analgesia while ventilated Optimize oxygenation through ventilation

22. Removal of any indwelling catheter considered to be a source of infection Drainage of a focal source of infection. Monitoring patient: – May require measures of central venous pressure and urinary output with a catheter Surgery may also be required: – E.g. wound debridement, abscess drainage. The duration of treatment is influenced by factors such as: – The site of tissue infection – The adequacy of surgical drainage – The patient's underlying disease – The antimicrobial susceptibility of the pathogen.

23. Monitoring  Once effective circulating volume has been restored, ongoing fluid requirements are guided by monitoring of tissue perfusion, including Mean arterial blood pressure target >5th percentile for age Capillary refill time Urine output Replacement of measured or estimated fluid losses Serial blood lactate levels If available and appropriate, measurement of: Arterial blood pressure Central venous pressure ScvO2 The mean arterial pressure target can be estimated as follows: mean arterial pressure (5th percentile at 50th height percentile) >1.5 x age in years + 40 .

24. Reference Weiss SL, Peters MJ, Alhazzani W, et al. Executive Summary: Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Pediatr Crit Care Med 2020; 21:186. Brun-Buisson C, Doyon F, Carlet J, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA 1995; 274:968. Gaines NN, Patel B, Williams EA, Cruz AT. Etiologies of septic shock in a pediatric emergency department population. Pediatr Infect Dis J 2012; 31:1203.