Small-volume 7.5% NaCl adenosine, lidocaine, and Mg2+ has multiple benefits during hypotensive and blood resuscitation in the pig following severe blood loss: rat to pig translation

Crit Care Med. 2014 May;42(5):e329-44. doi: 10.1097/CCM.0000000000000225.

Abstract

Objectives: Currently, there is no effective small-volume fluid for traumatic hemorrhagic shock. Our objective was to translate small-volume 7.5% NaCl adenosine, lidocaine, and Mg hypotensive fluid resuscitation from the rat to the pig.

Design: Pigs (35-40 kg) were anesthetized and bled to mean arterial pressure of 35-40 mm Hg for 90 minutes, followed by 60 minutes of hypotensive resuscitation and infusion of shed blood. Data were collected continuously.

Setting: University hospital laboratory.

Subjects: Female farm-bred pigs.

Interventions: Pigs were randomly assigned to a single IV bolus of 4 mL/kg 7.5% NaCl + adenosine, lidocaine and Mg (n = 8) or 4 mL/kg 7.5% NaCl (n = 8) at hypotensive resuscitation and 0.9% NaCl ± adenosine and lidocaine at infusion of shed blood.

Measurements and main results: At 60 minutes of hypotensive resuscitation, treatment with 7.5% NaCl + adenosine, lidocaine, and Mg generated significantly higher mean arterial pressure (48 mm Hg [95% CI, 44-52] vs 33 mm Hg [95% CI, 30-36], p < 0.0001), cardiac index (76 mL/min/kg [95% CI, 63-91] vs 47 mL/min/kg [95% CI, 39-57], p = 0.002), and oxygen delivery (7.6 mL O2/min/kg [95% CI, 6.4-9.0] vs 5.2 mL O2/min/kg [95% CI, 4.4-6.2], p = 0.003) when compared with controls. Pigs that received adenosine, lidocaine, and Mg/adenosine and lidocaine also had significantly lower blood lactate (7.1 mM [95% CI, 5.7-8.9] vs 11.3 mM [95% CI, 9.0-14.1], p = 0.004), core body temperature (39.3°C [95% CI, 39.0-39.5] vs 39.7°C [95% CI, 39.4-39.9]), and higher base excess (-5.9 mEq/L [95% CI, -8.0 to -3.8] vs -11.2 mEq/L [95% CI, -13.4 to -9.1]). One control died from cardiovascular collapse. Higher cardiac index in the adenosine, lidocaine, and Mg/adenosine and lidocaine group was due to a two-fold increase in stroke volume. Left ventricular systolic ejection times were significantly higher and inversely related to heart rate in the adenosine, lidocaine, and Mg/adenosine and lidocaine group. Thirty minutes after blood return, whole-body oxygen consumption decreased in pigs that received adenosine, lidocaine, and Mg/adenosine and lidocaine (5.7 mL O2/min/kg [95% CI, 4.7-6.8] to 4.9 mL O2/min/kg [95% CI, 4.2-5.8]), whereas it increased in controls (4.2 mL O2/min/kg [95% CI, 3.5-5.0] to 5.8 mL O2/min/kg [95% CI, 4.9-5.8], p = 0.02). After 180 minutes, pigs in the adenosine, lidocaine, and Mg/adenosine and lidocaine group had three-fold higher urinary output (2.1 mL//kg/hr [95% CI, 1.2-3.8] vs 0.7 mL//kg/hr [95% CI, 0.4-1.2], p = 0.001) and lower plasma creatinine levels.

Conclusion: Small-volume resuscitation with 7.5% NaCl + adenosine, lidocaine, and Mg/adenosine and lidocaine provided superior cardiovascular, acid-base, metabolic, and renal recoveries following severe hemorrhagic shock in the pig compared with 7.5% NaCl alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage
  • Animals
  • Blood Volume / drug effects
  • Disease Models, Animal
  • Drug Therapy, Combination / methods*
  • Female
  • Fluid Therapy / methods*
  • Hemoglobin A / analysis
  • Hypotension / drug therapy*
  • Hypotension / metabolism
  • Infusions, Intravenous
  • Lidocaine / administration & dosage
  • Magnesium / administration & dosage
  • Oxygen Consumption / drug effects
  • Rats
  • Rehydration Solutions / pharmacology
  • Shock, Hemorrhagic / drug therapy*
  • Shock, Hemorrhagic / metabolism
  • Sodium Chloride / administration & dosage
  • Stroke Volume / drug effects
  • Sus scrofa
  • Vasodilator Agents / administration & dosage*

Substances

  • Rehydration Solutions
  • Vasodilator Agents
  • Sodium Chloride
  • Hemoglobin A
  • Lidocaine
  • Magnesium
  • Adenosine