Table 3.
Clinical studies and animal models evaluating longitudinal cytokine response to trauma
| IL-6 | IL-10 | TNF | |||||
|---|---|---|---|---|---|---|---|
| Study (reference #) | Injury/Insult, n | Mean Peak (pg/mL) | Time Point | Mean Peak (pg/mL) | Time Point | Mean Peak (pg/mL) | Time Point |
| Kubiak 2011 [20] Animal (Insult): Swine (Trauma, IRI, Sepsis) Survival: 48 h |
Trauma (laparotomy) + IRI (SMA clamp × 30 min) + Sepsis (fecal clot) with passive drainage at 12 h. n = 5 | 23,702 | 36 h | 163 | 6 h | 852 | 48 h |
| Kinasewitz 2000 [30] Animal(Insult): NHP (Trauma, Sepsis) Survival: 14 days |
Trauma (laparotomy), Sepsis (E coli fibrin clot peritonitis). n = 5 (non-survivor) | ~ 22,000 | 4 h | ~ 31,000 (death) | 2 h | ||
| Trauma (laparotomy), Sepsis (E. coli fibrin clot peritonitis). n = 4 (signs of sepsis) | ~ 22,000 | 4 h | ~ 12,000 (sepsis) | 2 h | |||
| Trauma (laparotomy), Sepsis (E. coli fibrin clot peritonitis). n = 4 (well appearing) | ~ 10,000 | 4 h | ~ 12,000 (well) | 2 h | |||
| Martin 1997 [21] Clinical Study (Sepsis vs. Trauma and Survivors vs. Nonsurvivors) and (Sepsis vs. Trauma and Hemorrhage) |
Septic Shock (mean APACHE II score = 27) non-survivors n = 14 | 15,627 | arrival | 34 | 9th blood draw | ||
| Septic Shock (mean APACHE II score = 27) survivors n = 11 | ~ 4000 | arrival | ~ 20 | 3rd blood draw | |||
| Trauma (mean ISS = 27) non-survivors n = 7 | 600 | 8th blood draw | 30 | blood draw 13 | |||
| Trauma (mean ISS = 27) survivors n = 53 | ~ 200 | peak | ~ 20 | blood draw 11 | |||
| Trauma (mean ISS not reported) + Hemorrhagic Shock n = 8 | 420 | 2nd blood draw | ~ 30 | 8th blood draw | |||
| Jastrow 2009 [40] Clinical Study (Trauma +/− MOF) |
Trauma (mean ISS 26) with MOF. n = 11 | 7179 | 2–6 h | 239 | 2–6 h | 211 | 2–6 h |
| Trauma (mean ISS 25) with nonMOF. n = 37 | 427 | 6–10 h | 15 | 2–6 h | 0 | 2–6 h | |
| PHM Animal: NHP (Trauma, Hemorrhage, and Sepsis) Survival: 14 days |
Trauma (laparoscopic liver/bowel injury, flank soft tissue injury) + intra-abdominal hemorrhage/ sepsis × 2 h. n = 20 | 6860 | 4 h | 13,519 | 2 h | 321 | 24 h |
| THM Animal: NHP (Trauma and Hemorrhage) Survival: 14 days | Trauma (laparoscopic liver injury) + Hemorrhage (uncontrolled hemorrhage × 120 min)n = 5 | 1168 | 4 h | 588 | 2 h | 2 | 60 min |
| Sheppard 2017 [43] Animal: NHP (Trauma and Hemorrhage) Survival: 24 h |
Trauma (Lapartomy and Femur Fracture) + Decompensated Hemorrhage (pressure controlled) | ~ 750 | 6 h | ~ 450 | < 6 h | ||
| Trauma (Laparotomy and Femur Fracture) + 60 min Hemorrhage (Pressure Controlled) | ~ 400 | 6 h | ~ 650 | < 6 h | |||
| Deitch 1996 [41] Animal: NHP (Trauma and Hemorrhage vs. Trauma) Survival: 8 h |
Trauma (neck dissection and partial removal of clavicle) + Hemorrhage (40 mmHg × 3 h or reached -5 mEq Base Excess). n = 5 | ~ 350 | ~ 4 h | ||||
| Trauma (neck dissection and partial removal of clavicle) | ~ 100 | ~ 8 h | |||||
| Namas 2009 [38] Clinical Study (Trauma) |
Human Trauma (mean ISS 24) + Hemorrhagic Shock n = 4 (non-survivors) | 202a | within 6 h | 33a | within 6 h | 4a | within 6 h |
| Baker 2012 [35] Animal: Swine (Trauma vs. Hemorrhage vs. Trauma and Hemorrhage) Survival: 300 min |
Trauma (femur fracture and lung contusion) + Hemorrhage(20-30 mmHg × 60 min). n = 6 | ~ 170 | 2 h | ~ 15 | baseline | 133 | baseline |
| Trauma (femur fracture and lung contusion). n = 5 | ~ 170 | 5 h | ~ 100 | 45 min | ~ 300 | 60 min | |
| Hemorrhage(20-30 mmHg × 60 min)n = 5 | ~ 150 | 3 h | ~ 41 | < 15 min | ~ 290 | 45 min | |
| Namas 2009 [38] Animal (insult): Swine (Trauma and Hemorrhage vs. Hemorrhage) Survival: 2 h after resuscitation |
Trauma (anterolateral thoractomy and pericardial window) + Hemorrhage (MAP < 30 mmHg × 10 min, MAP < 20 mmHg for 10 s, or MAP>/= 30 × 90 min). n = 4 (non-survivors) | ~ 90 | 90 min | ~ 15 | 90 min | ~ 170 | 90 min |
| Hemorrhage (MAP < 30 mmHg × 10 min, MAP < 20 mmHg for 10 s, or MAP >/= 30 × 90 min). n = 3 (non-survivors) | ~ 1 | baseline | ~ 20 | 60 min | ~ 100 | baseline | |
| Trauma (anterolateral thoractomy and pericardial window) + Hemorrhage (MAP < 30 mmHg × 10 min, MAP < 20 mmHg for 10 s, or MAP>/= 30 × 90 min). n = 7 (survivors) | ~ 40 | 90 min | ~ 1 | baseline | ~ 240 | 90 min | |
| Hemorrhage (MAP < 30 mmHg × 10 min, MAP < 20 mmHg for 10 s, or MAP >/= 30 × 90 min). n = 9 (survivors) | ~ 30 | baseline | 5 | baseline | ~ 600 | 0 min | |
Literature review of animal and clinical studies comparing trauma +/− sepsis +/− hemorrhagic insults
~Serum cytokine level (pg/mL) approximated from article’s figure
NHP nonhuman primate, NMRC Naval Medical Research Center, PHM Polytrauma and Hemorrhage Model, THM Trauma and Hemorrhage Model, IRI Ischemia Reperfusion Injury, SMA Superior Mesenteric Artery
amean cytokine value within first 6 h of injury