Effects of a combination hemoglobin based oxygen carrier–hypertonic saline solution on oxygen transport in the treatment of traumatic shock

Leong, Benjamin Sieu Hon; Reynolds, Penny S.; Tiba, Mohamad H.; Holbert, William H.; Draucker, Gerard T.; Medina, Juliana; Barbee, R. Wayne; White, Nathan J.; Ward, Kevin R.

doi:10.1016/j.resuscitation.2011.03.018

Cited by 9 publications

(9 citation statements)

References 23 publications

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“…It has been successfully used in prior cardiotoxic drug models performed at our institution and hemorrhagic swine models [26][27][28][29]. We tested the alphachloralose in several animals prior to initiation of the full study and confirmed a lack of direct hemodynamic effect.…”

Section: Limitationsmentioning

confidence: 74%

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock

et al. 2016

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Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/ min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre-and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.

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Section: Limitationsmentioning

confidence: 74%

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock

et al. 2016

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“…The target MAP during hemorrhagic shock was 5 mmHg higher for pigs than it was for the rats (35 Vs. 30 mmHg). This was to prevent myocardial injury in the pigs that would otherwise occur during very low MAPs (10). Plasma lactate accumulation was used as a marker for reporting oxygen debt in both models, which served as our metabolic endpoint of shock severity (11–14).…”

Section: Discussionmentioning

confidence: 99%

“…The procedures were conducted as previously described, except lactate controlled endpoint were used (10). …”

Section: Methodsmentioning

confidence: 99%

Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock

Plant

Limkemann

Liebrecht

et al. 2016

Journal of Trauma and Acute Care Surgery

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Introduction Polyethylene glycol-20k (PEG-20k) is highly effective for low volume resuscitation (LVR) by increasing tolerance to the low volume state. In our rodent shock model, PEG-20k increased survival and expanded the “golden hour” 16-fold compared to saline. The molecular mechanism is largely attributed to normalizations in cell and tissue fluid shifts after low flow ischemia resulting in efficient microvascular exchange. The objective of this study was to evaluate PEG-20k as a low volume resuscitation solution for hemorrhagic shock in a pre-clinical model. Methods Anesthetized male Yorkshire pigs (30–40 kg) were hemorrhaged to a MAP of 35–40 mmHg. Once lactate reached 7 mM/L, either saline (n = 5) or 10% PEG-20k (n = 5) was rapidly infused at 10% calculated blood volume. The primary outcome was LVR time, defined by the time from LVR administration to the time when lactate again reached 7 mM/L. Other outcomes measured included: MAP, heart rate (HR), cardiac output (CO), mixed venous oxygen saturation (SvO2), splanchnic blood flow, and hemoglobin. Results Relative to saline, PEG-20k given after controlled hemorrhage increased LVR time by 16-fold, a conservative estimate given that the lactate never rose after LVR in the PEG-20k group. Survival was 80% for PEG-20k LVR compared to 0% for the saline controls (P<0.05). PEG-20k also significantly decreased HR after hemorrhage and increased CO, MAP, splanchnic flow, and SvO2. Falling hemoglobin concentrations suggested sizable hemodilution from fluid shifts into the intravascular compartment. Conclusions In a pre-clinical model of controlled hemorrhagic shock, PEG-20k-based LVR solution increased tolerance to the shock state 16-fold compared to saline. PEG-20k is a superior crystalloid for low volume resuscitation that may increase safe transport times in the prehospital setting and find use in hospital emergency departments and operating rooms for patients awaiting volume replacement or normalization of cell, tissue, and compartment fluid volumes.

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“…The University (of Michigan) Committee on Use and Care of Animals approved this study, which adhered to the Guide for the Care and Use of Laboratory Animals (National Research Council, revised 2011). Details of this swine model of traumatic shock have been previously described which demonstrate the stability and consistency of this model (13). In brief, this model of controlled hemorrhagic shock is performed in the setting of tissue trauma targeting oxygen debt as a primary endpoint for hemorrhage.…”

Section: Methodsmentioning

confidence: 99%

Whole Blood Redox Potential Correlates With Progressive Accumulation of Oxygen Debt and Acts as A Marker of Resuscitation in A Swine Hemorrhagic Shock Model

Daniels

Jun

Tiba

et al. 2018

Shock

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Introduction Oxidation-reduction reactions involve electron exchanges that require optimal balance for proper cell function. This balance is measured via redox potential and reflects oxidative stress. Despite the critical role of oxidative stress in critical illness and injury, little is known regarding redox potential. We hypothesize redox potential measurements will correlate with accumulation of O2 debt produced by hemorrhage over time. Methods Ten swine were studied using a polytrauma hemorrhagic shock model. Whole blood and plasma redox potential measures were obtained at defined stages of O2 debt (20, 40, 60, 80mL/kg), and through resuscitation. Redox potential was determined by measuring open circuit potential using novel gold nanoporous electrodes with Ag/AgCl reference. Results Whole blood redox potential showed negative change as O2 debt accumulated, exhibiting positive response during resuscitation, and correlated with O2 debt across all animals (p<0.001). Redox potential changes throughout O2 debt accrual were significant compared to baseline (p≤0.05), and at end resuscitation compared to O2 debt 60 mL/kg (p=0.05) and 80 mL/kg (p=0.02). Whole blood redox potential measures also correlated with oxygen extraction ratio, ScvO2, and lactic acid, appearing very sensitive to acute changes. Plasma RP showed no correlation with O2 debt. Conclusions Whole blood redox potential demonstrates significant correlation to O2 debt at all stages in this model. These results set the stage for further study of redox potential as a direct measure of oxidative stress and potential clinical tool. Given redox potential plasma performance, these measures should be made in whole blood versus plasma.

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Effects of a combination hemoglobin based oxygen carrier–hypertonic saline solution on oxygen transport in the treatment of traumatic shock

Cited by 9 publications

References 23 publications

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock

Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock

Whole Blood Redox Potential Correlates With Progressive Accumulation of Oxygen Debt and Acts as A Marker of Resuscitation in A Swine Hemorrhagic Shock Model

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