Page 134 - JSOM Fall 2020

lactate. After whole body ➝ kidney brain
➝ cardiac contractility ➝ systolic ejection time, lactate, and 3-fold systolic pressure dP/dt min (less stiff cerebral O 2 brain glycerol (60%), ➝ cortical expression of hypoxia mean pulmonary arterial lactate, ➝ ➝ urinary output

Other Major Outcomes Reduced postshock fluid requirements in ALM-treated ➝ SVR. After 30-min hypotension, shed blood was returned with another AL bolus that led to 27% ➝ in whole body O 2 consumption and improved kidney creatinine). 35 After 60-min hypotensive resuscitation, ALM animals returning shed blood, ALM animals had ➝ 1.43L Hextend (3 × 500mL bolus) was superior to any other treatment to resuscitate. ALM was inferior. MAP. Kidney

animals was associated with and function ( ➝ GFR, ➝ had 2-fold ➝ CO and SV, maintained ventriculoarterial coupling, ➝ O 2 consumption (15%), ➝ output. One control died. 36 Controls and ALM groups showed ➝ and ➝ among groups. 39 ALM animals had heart), ➝ consumption (28%), ➝ lactate (47%), and ➝ increased urine output. 38 state with ➝ ventriculoarterial coupling, ➝ pressure, maintained tissue blood flow, ➝ whole body O

Coagulopathy Inflammation Model did not induce inflammatory response (no difference in cytokine levels) Not measured Hextend led to platelet TIC and ➝ aggregation. ALM corrected coagulopathy (ROTEM, STAGO) ALM IL-6/IL-10 ratio 50% lower than ➝ controls. ALM fibrinogen. After drip control antiplasmin fell 20%. ALM-LPS–infused TnF-α animals ➝ leukocyte (90 min) ➝ superoxide production

TABLE 3 Summary of the Effect of ALM Therapy in Pig Models After Hemorrhagic Shock and Endotoxemia (2012 to Present)

IV Drip No No 0.5mL/kg/hr (1–2 hours) or 3mL/kg/hr (2 hours) 3mL/kg/hr for 4 hours 5 hours (high dose 1 hour, low dose 4 hours) SVR = systemic vascular resistance; CO = cardiac output; SV = stroke volume; LPS = lipopolysaccharide; MAP = mean arterial pressure; ROTEM = rotational thromboelastometry; TIC = trauma-induced

Hypotensive Resuscitation b 7.5% NaCl ALM in Ringer’s acetate led to 40% less fluid to raise MAP to 50mmHg 4mL/kg bolus 7.5% NaCl ALM At 60 min MAP 48mmHg vs 33mmHg (controls) Hextend/lactated Ringer’s: 500mL bolus at a time, 3% NaCl ALM 2 or 4mL/kg bolus 4mL/kg bolus c 3% NaCl ALM At 4 hours MAP 47mmHg (ALM) vs 62mmHg (controls) 0.9% NaCl ALM maintained constant 47mmHg MAP. Controls were 80–90mmHg

Bleed/Shock Time (min) 90 90 Variable (40 to 81 min) Free to bleed — c Hypertonic saline with ALM was decreased from 7.5% to 3.0% since the latter is FDA approved for clinical use.

Study Duration a / Anesthesia Acute 7 hours ventilator midazolam/ ketamine/fentanyl Acute 4 hours ventilator midazolam/ ketamine/fentanyl Acute 4 hours ventilator 1% to 3% isoflurane Telazol, Buprenex Acute 6 hours ventilator midazolam/ ketamine/propofol/ fentanyl Acute 6 hours ventilator midazolam/ ketamine/ fentanyl b Ringer’s acetate with 20mL 7.5% NaCl or Ringer’s acetate with 20mL 7.5% NaCl ALM.

Hemorrhagic Shock ~40-kg female pigs pressure controlled (74% blood loss, nonsplenectomized) 35- to 40-kg female pigs pressure controlled (73% blood loss, nonsplenectomized) 70- to 90-kg male pigs pressure controlled (44% to 60% blood loss) 59-kg female pigs noncompressible hemorrhage (removed 0.45L blood and laparoscopic liver resection) 40-kg female pigs LPS infusion (1mg/kg/hr) with and without ALM a Study duration

Study 1 2 3 4 Endotoxemia (LPS) 5 coagulopathy.

132 | JSOM Volume 20, Edition 3 / Fall 2020