Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock

Summary

Presented here is a protocol to measure renal oxygenation in the medulla and noninvasive urine oxygen partial pressure in a hemorrhagic shock porcine model to establish urine oxygen partial pressure as an early indicator of acute kidney injury (AKI) and a novel resuscitative endpoint.

Abstract

Up to 50% of patients with trauma develop acute kidney injury (AKI), in part due to poor renal perfusion after severe blood loss. AKI is currently diagnosed based on a change in serum creatinine concentration from baseline or prolonged periods of decreased urine output. Unfortunately, baseline serum creatinine concentration data is unavailable in most patients with trauma, and current estimation methods are inaccurate. In addition, serum creatinine concentration may not change until 24-48 h after the injury. Lastly, oliguria must persist for a minimum of 6 h to diagnose AKI, making it impractical for early diagnosis. AKI diagnostic approaches available today are not useful for predicting risk during the resuscitation of patients with trauma. Studies suggest that urinary partial pressure of oxygen (PuO₂) may be useful for assessing renal hypoxia. A monitor that connects the urinary catheter and the urine collection bag was developed to measure PuO₂ noninvasively. The device incorporates an optical oxygen sensor that estimates PuO₂ based on luminescence quenching principles. In addition, the device measures urinary flow and temperature, the latter to adjust for confounding effects of temperature changes. Urinary flow is measured to compensate for the effects of oxygen ingress during periods of low urine flow. This article describes a porcine model of hemorrhagic shock to study the relationship between noninvasive PuO₂, renal hypoxia, and AKI development. A key element of the model is the ultrasound-guided surgical placement in the renal medulla of an oxygen probe, which is based on an unsheathed optical microfiber. PuO₂ will also be measured in the bladder and compared to the kidney and noninvasive PuO₂ measurements. This model can be used to test PuO₂ as an early marker of AKI and assess PuO₂ as a resuscitative endpoint after hemorrhage that is indicative of end-organ rather than systemic oxygenation.

Introduction

Acute kidney injury (AKI) affects up to 50% of patients with trauma admitted to the intensive care unit¹. Patients who develop AKI tend to have longer hospital and intensive care unit lengths of stay and a threefold greater risk of mortality^2,3,4. Currently, AKI is most commonly defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, which are based on changes in serum creatinine concentration from baseline or periods of prolonged oliguria⁵. Baseline creatinine concentration data are unavailable in most patie....

Protocol

The Institutional Animal Care and Use Committee of the University of Utah approved all experimental protocols described here. Prior to the experiment, a total of 12 castrated male or non-pregnant female Yorkshire swine weighing 50-75 kg and between 6-8 months old were acclimated in their enclosures for at least 7 days. During this period, all care is directed by a veterinarian and in accordance with the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act Regulations and Standards. The animals are .......

Discussion

AKI is a common complication in patients with trauma, and currently, there is no validated bedside monitor for kidney tissue oxygenation, which could enable earlier AKI detection and guide potential interventions. This manuscript describes the use and instrumentation of a porcine hemorrhagic shock model to establish noninvasive PuO₂ as an early indicator of AKI and a novel resuscitation endpoint in trauma settings.

One of the distinct advantages of this porcine model is the ability .......

Materials

Name	Company	Catalog Number	Comments
1/8" PVC tubing	Qosina	SKU: T4307	Part of noninvasive PuO2 monitor
3/16" PVC tubing	Qosina	SKU: T4310	Part of noninvasive PuO2 monitor
3/8" TPE tubing	Qosina	SKU: T2204	Part of noninvasive PuO2 monitor
3/32" (1), 1/8" (1), 5/32" (1) drill bit	Dewalt	N/A	For building noninvasive PuO2 monitor
Biocompatible Glue	Masterbond	EP30MED	Part of noninvasive PuO2 monitor
Bladder PuO2 sensor	Presens	DP-PSt3	Oxygen dipping probe
Bladder oxygen measurement device	Presens	Fibox 4	Stand-alone fiber optic oxygen meter
Chlorhexidine 4% scrub	Vetone	N/A	For scrubbing insertion or puncture sites
Conical connector with female luer lock	Qosina	SKU: 51500	Part of noninvasive PuO2 monitor
Cuffed endotracheal tube	Vetone	600508	For sedating the subject and providing respiratory support
Euthanasia solution (pentobarbital sodium|pheyntoin sodium)	Vetone	11168	For euthanasia after completion of experiment
General purpose temperature probe, 400 series thermistor	Novamed	10-1610-040	Part of noninvasive PuO2 monitor
HotDog veterinary warming system	HotDog	V106	For controlling subject temperature during experiment
Invasive tissue oxygen measurement device	Optronix	N/A	OxyLite™ oxygen monitors
Invasive tissue oxygen sensor	Optronix	NX-BF/OT/E	Oxygen/Temperature bare-fibre sensor
Isoflurane	Vetone	501017	To maintain sedation throughout the experiment
Isotonic crystalloid solution	HenrySchein	1537930 or 1534612	Used during resuscitation in the critical care period
Liquid flow sensor	Sensirion	LD20-2600B	Part of noninvasive PuO2 monitor
Male luer lock to barb connector	Qosina	SKU: 11549	Part of noninvasive PuO2 monitor
Male to male luer connector	Qosina	SKU: 20024	Part of noninvasive PuO2 monitor
Norepinephrine	HenrySchein	AIN00610	Infusion during resuscitation
Noninvasive oxygen measurement device	Presens	EOM-O2-mini	Electro optical module transmitter for contactless oxygen measurements
Non-vented male luer lock cap	Qosina	SKU: 65418	Part of noninvasive PuO2 monitor
O2 sensor stick	Presens	SST-PSt3-YOP	Part of noninvasive PuO2 monitor
PowerLab data acquisition platform	AD Instruments	N/A	For data collection
REBOA catheter	Certus Critical Care	N/A	Used in experimental protocol
Super Sheath arterial catheters (5 Fr, 7 Fr, 9 Fr)	Boston Scientific	C1894	for intravascular access
Suture	Ethicon	C013D	For securing catheter to skin and closing incisions
T connector, all female luer locks	Qosina	SKU: 88214	Part of noninvasive PuO2 monitor