Critical Care Medicine  |   November 2019
Effect of Polyethylene-glycolated Carboxyhemoglobin on Renal Microcirculation in a Rat Model of Hemorrhagic Shock
Author Notes
  • From the Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (P.G., B.E., M.H., C.I.); INSERM U1116, University of Lorraine, Vandoeuvre-Les-Nancy, France (P.G.); the Department of Anesthesiology and Critical Care Medicine, University Hospital of Nancy, Nancy, France (P.G.); the Department of Intensive Care Adults, Erasmus MC, University Medical Center, Rotterdam, Rotterdam, The Netherlands (B.E., J.B., C.I.); the Department of Biology, Faculty of Science, University of Istanbul, Istanbul, Turkey (A.K.); Prolong Pharmaceuticals, South Plainfield, New Jersey (R.J.); the Department of Pulmonology and Critical Care, Columbia University Medical Center, New York, New York (J.B.); and the Department of Intensive Care, Pontifical Catholic University of Chile, Santiago, Chile (J.B.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • P.G. and B.E. contributed equally to this article.
    P.G. and B.E. contributed equally to this article.×
  • Submitted for publication December 27, 2018. Accepted for publication July 3, 2019.
    Submitted for publication December 27, 2018. Accepted for publication July 3, 2019.×
  • Address correspondence to Dr. Guerci: Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. phil.guerci@gmail.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Basic Science / Coagulation and Transfusion / Critical Care / Renal and Urinary Systems / Electrolyte Balance
Critical Care Medicine   |   November 2019
Effect of Polyethylene-glycolated Carboxyhemoglobin on Renal Microcirculation in a Rat Model of Hemorrhagic Shock
Anesthesiology 11 2019, Vol.131, 1110-1124. doi:10.1097/ALN.0000000000002932
Anesthesiology 11 2019, Vol.131, 1110-1124. doi:10.1097/ALN.0000000000002932
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • The optimal fluid for resuscitation of hemorrhagic shock (crystalloid, colloid, or hemoglobin-containing) and mitigation of acute kidney injury is unknown

What This Article Tells Us That Is New:

  • In a rat model of hemorrhagic shock comparing fluid resuscitation with blood, diluted blood, hydroxyethyl starch, or polyethylene-glycolated carboxyhemoglobin, all fluids restored urine output and creatinine clearance, but only blood and diluted blood improved renal Po2

  • Postresuscitation histologic renal tubular damage was increased compared with nonresuscitated rats but slightly less with blood, diluted blood, and polyethylene-glycolated carboxyhemoglobin compared with hydroxyethyl starch

  • Restoration of circulatory hemodynamics and kidney microcirculatory Po2 was comparable with polyethylene-glycolated carboxyhemoglobin and balanced hydroxyethyl starch solution

Background: Primary resuscitation fluid to treat hemorrhagic shock remains controversial. Use of hydroxyethyl starches raised concerns of acute kidney injury. Polyethylene-glycolated carboxyhemoglobin, which has carbon monoxide–releasing molecules and oxygen-carrying properties, was hypothesized to sustain cortical renal microcirculatory Po2 after hemorrhagic shock and reduce kidney injury.

Methods: Anesthetized and ventilated rats (n = 42) were subjected to pressure-controlled hemorrhagic shock for 1 h. Renal cortical Po2 was measured in exposed kidneys using a phosphorescence quenching method. Rats were randomly assigned to six groups: polyethylene-glycolated carboxyhemoglobin 320 mg · kg−1, 6% hydroxyethyl starch (130/0.4) in Ringer’s acetate, blood retransfusion, diluted blood retransfusion (~4 g · dl−1), nonresuscitated animals, and time control. Nitric oxide and heme oxygenase 1 levels were determined in plasma. Kidney immunohistochemistry (histologic scores of neutrophil gelatinase-associated lipocalin and tumor necrosis factor-α) and tubular histologic damages analyses were performed.

Results: Blood and diluted blood restored renal Po2 to 51 ± 5 mmHg (mean difference, −18; 95% CI, −26 to −11; P < 0.0001) and 47 ± 5 mmHg (mean difference, −23; 95% CI, −31 to −15; P < 0.0001), respectively, compared with 29 ± 8 mmHg for hydroxyethyl starch. No differences between polyethylene-glycolated carboxyhemoglobin and hydroxyethyl starch were observed (33 ± 7 mmHg vs. 29 ± 8 mmHg; mean difference, −5; 95% CI, −12 to 3; P = 0.387), but significantly less volume was administered (4.5 [3.3–6.2] vs. 8.5[7.7–11.4] ml; mean rank difference, 11.98; P = 0.387). Blood and diluted blood increased the plasma bioavailability of nitric oxide compared with hydroxyethyl starch (mean rank difference, −20.97; P = 0.004; and −17.13; P = 0.029, respectively). No changes in heme oxygenase 1 levels were observed. Polyethylene-glycolated carboxyhemoglobin limited tubular histologic damages compared with hydroxyethyl starch (mean rank difference, 60.12; P = 0.0012) with reduced neutrophil gelatinase-associated lipocalin (mean rank difference, 84.43; P < 0.0001) and tumor necrosis factor-α (mean rank difference, 49.67; P = 0.026) histologic scores.

Conclusions: Polyethylene-glycolated carboxyhemoglobin resuscitation did not improve renal Po2 but limited tubular histologic damages and neutrophil gelatinase-associated lipocalin upregulation after hemorrhage compared with hydroxyethyl starch, whereas a lower volume was required to sustain macrocirculation.