Method Article

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

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DOI:

10.3791/64461

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October 28th, 2022

 ,  ,  , 
1Department of Biomedical Engineering, University of Utah, 2Department of Emergency Medicine, University of Utah, 3Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 4Department of Anesthesiology, University of Utah, 5Geriatric Research, Education, and Clinical Centre, VAMC

In This Article

Erratum Notice

Important: There has been an erratum issued for this article. View Erratum Notice

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 mortality2,3,4. 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....

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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 fasted overnight prior to induction of anesthesia but are allowed free access to water.

1. Sensor assembly<....

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Results

Figure 1 shows an image of the noninvasive PuO2 monitor described in this manuscript. Figure 2 shows a plot of MAP and noninvasive PuO2 measurements in a single subject during an experiment similar to the described porcine hemorrhage model. At the start of the experiment, as hemorrhage was initiated, there was a drop in MAP and PuO2. Following the initial decline in PuO2 it gradually increased until after the REBOA bal.......

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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 .......

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Disclosures

N. Silverton, K. Kuck, and L. Lofgren are inventors of a patent and patent application surrounding the noninvasive monitor used in this study. This prototype is under development for commercial consideration by N. Silverton and K. Kuck, but as of yet, no commercial activity has occurred. The other authors declare no competing interests. The interpretation and reporting of these data are the responsibility of the authors alone.

Acknowledgements

The work in this grant is funded by the University of Utah Clinical and Translational Science Institute through the Translational and Clinical Studies Pilot Program and the Department of Defense office of the Congressionally Directed Medical Research Programs (PR192745).

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
1/8" PVC tubingQosinaSKU: T4307Part of noninvasive PuO2 monitor
3/16" PVC tubingQosinaSKU: T4310Part of noninvasive PuO2 monitor
3/8" TPE tubing QosinaSKU: T2204Part of noninvasive PuO2 monitor
3/32" (1), 1/8" (1), 5/32" (1) drill bitDewaltN/AFor building noninvasive PuO2 monitor
Biocompatible GlueMasterbondEP30MEDPart of noninvasive PuO2 monitor
Bladder PuO2 sensorPresensDP-PSt3Oxygen dipping probe
Bladder oxygen measurement devicePresensFibox 4Stand-alone fiber optic oxygen meter
Chlorhexidine 4% scrubVetoneN/AFor scrubbing insertion or puncture sites
Conical connector with female luer lockQosinaSKU: 51500Part of noninvasive PuO2 monitor
Cuffed endotracheal tubeVetone600508For sedating the subject and providing respiratory support
Euthanasia solution (pentobarbital sodium|pheyntoin sodium)Vetone11168For euthanasia after completion of experiment
General purpose temperature probe, 400 series thermistorNovamed10-1610-040Part of noninvasive PuO2 monitor
HotDog veterinary warming systemHotDogV106For controlling subject temperature during experiment
Invasive tissue oxygen measurement deviceOptronixN/AOxyLite™ oxygen monitors
Invasive tissue oxygen sensorOptronixNX-BF/OT/EOxygen/Temperature bare-fibre sensor
IsofluraneVetone501017To maintain sedation throughout the experiment
Isotonic crystalloid solutionHenrySchein1537930 or 1534612Used during resuscitation in the critical care period
Liquid flow sensorSensirionLD20-2600BPart of noninvasive PuO2 monitor
Male luer lock to barb connectorQosinaSKU: 11549Part of noninvasive PuO2 monitor
Male to male luer connectorQosinaSKU: 20024Part of noninvasive PuO2 monitor
NorepinephrineHenryScheinAIN00610Infusion during resuscitation
Noninvasive oxygen measurement devicePresensEOM-O2-miniElectro optical module transmitter for contactless oxygen measurements
Non-vented male luer lock cap QosinaSKU: 65418Part of noninvasive PuO2 monitor
O2 sensor stickPresensSST-PSt3-YOPPart of noninvasive PuO2 monitor
PowerLab data acquisition platformAD InstrumentsN/AFor data collection
REBOA catheterCertus Critical CareN/AUsed in experimental protocol
Super Sheath arterial catheters (5 Fr, 7 Fr, 9 Fr)Boston ScientificC1894for intravascular access
SutureEthiconC013DFor securing catheter to skin and closing incisions
T connector, all female luer locksQosinaSKU: 88214Part of noninvasive PuO2 monitor

References

  1. Gomes, E., Antunes, R., Dias, C., Araújo, R., Costa-Pereira, A. Acute kidney injury in severe trauma assessed by RIFLE criteria: a common feature without implications on mortality. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 18, 1(2010).
  2. Bihorac, A., et al.

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Erratum


Formal Correction: Erratum: Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock
Posted by JoVE Editors on 5/09/2023. Citeable Link.

An erratum was issued for: Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock. The Protocol section was updated.

Step 2.3.1 - 2.3.1.2 of the Protocol was updated from:

  1. Measure PuO2 in the bladder.
    1. Remove all air from the bladder by slowly squeezing the bladder while ensuring urine does not leak out.
    2. Place the tip of the luminescence quenching-based PuO2 sensor in the bladder via a cystotomy, similar to the catheter.
    3. Connect the fiber optic cable from the bladder sensor to the data collection device.

to:

  1.  Measure PuO2 at the outlet of the bladder
    1. Identify the balloon on the catheter. Just below the balloon make an incision along the long axis of the catheter, ensuring that you do not cut the lumen that connects to the balloon. 
    2. After making the incision, insert a t-connector that contains the sensing material into the incision. 
    3. Use tissue glue to secure the t-connector in place. 
    4. Connect the fiber optic cable from the bladder data collection device to the connector that contains the sensing material. 

Step 2.3.2.2 - 2.3.2.7 of the Protocol was updated from:

  1. Make a flank incision large enough to expose the kidney (approx. 2-3 in) on the side of the pig at approximately the same location where the kidney was identified.
  2. With the tips of a retractor together, introduce the retractor into the incision and then spread the tips of the retractor to expose the kidney.
  3. Use a micro-manipulator or similar tool to hold the oxygen probe steady. If possible, attach this tool to the end of an articulating arm.
  4. Attach the other end of the articulating arm to the surgical table so that the other end that will hold the oxygen probe is near the opened incision. If the tool that is used to hold the oxygen probe is not connected to an articulating arm, position the tool so the oxygen sensor is near the opened incision and is stable.
  5. Unlock all articulating joints of the arm. Using ultrasound, place the tip of the oxygen probe in the medulla region of the kidney. Lock all articulating joints on the arm.
  6. After confirming placement of the tip of the sensor in the medulla with ultrasound, use the micromanipulator to retract the needle housing the luminescence-based oxygen sensor. Connect the other end of the sensor to the data collection device connected to the computer running the data collection software. Start recording.

to:

  1. Move the bowel so that you have a clear line of site and access to the entire kidney. 
  2. Insert the sensor into 2" 18 gauge catheter. Adjust the luer lock connector on the sensor so that the tip of the sensor is exposed. Remove the catheter and place it over an 18 gauge needle.
  3. Place the 18 gauge needle and 2 in catheter into the renal medulla under ultrasound guidance.
  4. Remove the needle, keeping the catheter in place. Thread the tissue sensor through the catheter and use the luer lock to connect the sensor to the catheter. 
  5. Use tissue glue to secure the catheter in place. 
  6. Connect the tissue sensor to the data collection box.

The Table of Materials was updated from:

NameCompanyCatalog NumberComments
1/8" PVC tubingQosinaSKU: T4307Part of noninvasive PuO2 monitor
3/16" PVC tubingQosinaSKU: T4310Part of noninvasive PuO2 monitor
3/32" (1), 1/8" (1), 5/32" (1) drill bitDewaltN/AFor building noninvasive PuO2 monitor
3/8" TPE tubing QosinaSKU: T2204Part of noninvasive PuO2 monitor
Biocompatible GlueMasterbondEP30MEDPart of noninvasive PuO2 monitor
Bladder oxygen measurement devicePresensFibox 4Stand-alone fiber optic oxygen meter
Bladder PuO2 sensorPresensDP-PSt3Oxygen dipping probe
Chlorhexidine 4% scrubVetoneN/AFor scrubbing insertion or puncture sites
Conical connector with female luer lockQosinaSKU: 51500Part of noninvasive PuO2 monitor
Cuffed endotracheal tubeVetone600508For sedating the subject and providing respiratory support
Euthanasia solution (pentobarbital sodium|pheyntoin sodium)Vetone11168For euthanasia after completion of experiment
General purpose temperature probe, 400 series thermistorNovamed10-1610-040Part of noninvasive PuO2 monitor
Hemmtop Magic Arm 11 inchAmazonB08JTZRKYNHolding invasive oxygen sensor in place
HotDog veterinary warming systemHotDogV106For controlling subject temperature during experiment
Invasive tissue oxygen measurement devicePresensOxy-1 ST Compact oxygen transmitter
Invasive tissue oxygen sensorPresensPM-PSt7Profiling oxygen microsensor
IsofluraneVetone501017To maintain sedation throughout the experiment
Isotonic crystalloid solutionHenrySchein1537930 or 1534612Used during resuscitation in the critical care period
Liquid flow sensorSensirionLD20-2600BPart of noninvasive PuO2 monitor
Male luer lock to barb connectorQosinaSKU: 11549Part of noninvasive PuO2 monitor
Male to male luer connectorQosinaSKU: 20024Part of noninvasive PuO2 monitor
Noninvasive oxygen measurement devicePresensEOM-O2-miniElectro optical module transmitter for contactless oxygen measurements
Non-vented male luer lock capQosinaSKU: 65418Part of noninvasive PuO2 monitor
NorepinephrineHenryScheinAIN00610Infusion during resuscitation
O2 sensor stickPresensSST-PSt3-YOPPart of noninvasive PuO2 monitor
PowerLab data acquisition platformAD InstrumentsN/AFor data collection
REBOA catheterCertus Critical CareN/AUsed in experimental protocol
Super Sheath arterial catheters (5 Fr, 7 Fr, 9 Fr)Boston ScientificC1894For intravascular access
SutureEthiconC013DFor securing catheter to skin and closing incisions
T connector, all female luer locksQosinaSKU: 88214Part of noninvasive PuO2 monitor

to:

NameCompanyCatalog NumberComments
1/8" PVC tubingQosinaSKU: T4307Part of noninvasive PuO2 monitor
3/16" PVC tubingQosinaSKU: T4310Part of noninvasive PuO2 monitor
3/8" TPE tubing QosinaSKU: T2204Part of noninvasive PuO2 monitor
3/32" (1), 1/8" (1), 5/32" (1) drill bitDewaltN/AFor building noninvasive PuO2 monitor
Biocompatible GlueMasterbondEP30MEDPart of noninvasive PuO2 monitor
Bladder PuO2 sensorPresensDP-PSt3Oxygen dipping probe
Bladder oxygen measurement devicePresensFibox 4Stand-alone fiber optic oxygen meter
Chlorhexidine 4% scrubVetoneN/AFor scrubbing insertion or puncture sites
Conical connector with female luer lockQosinaSKU: 51500Part of noninvasive PuO2 monitor
Cuffed endotracheal tubeVetone600508For sedating the subject and providing respiratory support
Euthanasia solution (pentobarbital sodium|pheyntoin sodium)Vetone11168For euthanasia after completion of experiment
General purpose temperature probe, 400 series thermistorNovamed10-1610-040Part of noninvasive PuO2 monitor
HotDog veterinary warming systemHotDogV106For controlling subject temperature during experiment
Invasive tissue oxygen measurement deviceOptronixN/AOxyLite™ oxygen monitors
Invasive tissue oxygen sensorOptronixNX-BF/OT/EOxygen/Temperature bare-fibre sensor
IsofluraneVetone501017To maintain sedation throughout the experiment
Isotonic crystalloid solutionHenrySchein1537930 or 1534612Used during resuscitation in the critical care period
Liquid flow sensorSensirionLD20-2600BPart of noninvasive PuO2 monitor
Male luer lock to barb connectorQosinaSKU: 11549Part of noninvasive PuO2 monitor
Male to male luer connectorQosinaSKU: 20024Part of noninvasive PuO2 monitor
NorepinephrineHenryScheinAIN00610Infusion during resuscitation
Noninvasive oxygen measurement devicePresensEOM-O2-miniElectro optical module transmitter for contactless oxygen measurements
Non-vented male luer lock cap QosinaSKU: 65418Part of noninvasive PuO2 monitor
O2 sensor stickPresensSST-PSt3-YOPPart of noninvasive PuO2 monitor
PowerLab data acquisition platformAD InstrumentsN/AFor data collection
REBOA catheterCertus Critical CareN/AUsed in experimental protocol
Super Sheath arterial catheters (5 Fr, 7 Fr, 9 Fr)Boston ScientificC1894for intravascular access
SutureEthiconC013DFor securing catheter to skin and closing incisions
T connector, all female luer locksQosinaSKU: 88214Part of noninvasive PuO2 monitor

Tags

Hemorrhagic Shock ModelAcute Kidney InjuryUrine Oxygen Partial PressureNoninvasive PuO2 MonitoringRenal Medulla OxygenationOptical Oxygen SensorReboa CatheterCentral Venous Pressure

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