Publications by authors named "Ryan Inocencio"

7 Publications

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I-TRACH: Validating A Tool for Predicting Prolonged Mechanical Ventilation.

J Intensive Care Med 2018 Oct 30;33(10):567-573. Epub 2016 Nov 30.

1 Department of Pulmonary, Critical Care and Sleep Medicine, Walter Reed National Military Medical Center, Bethesda, MD, USA.

Purpose: We previously developed a bedside model (I-TRACH), which used commonly obtained data at the time of intubation to predict the duration of mechanical ventilation (MV). We now sought to validate this in a prospective trial.

Methods: A prospective, observational study of 225 consecutive adult medical intensive care unit patients requiring MV. Utilizing the original 6 variables used in the I-TRACH model (Intubation in the ICU, Tachycardia [heart rate > 110], Renal dysfunction [blood urea nitrogen > 25], Acidemia [pH < 7.25], Creatinine [>2.0 or >50% increase from baseline values], and decreased HCO [<20]), we (1) confirmed that these were still predictive of length of MV by multivariate analysis and (2) assessed the correlation between the number of criteria met and the subsequent duration of MV. In addition, we compared the performance of I-TRACH to Acute Physiology Age Chronic Health Evaluation-II and III, Sequential Organ Failure Assessment, and Acute Physiology Score as predictors of length of MV.

Results: Mean age was 62.6 ± 18.7 years, with a mean duration of MV of 5.8 ± 5.7 days. The number of I-TRACH criteria met directly correlated with the duration of MV. Individuals with ≥4 criteria were significantly more likely to require MV >7 and >14 days. Similarly, those who remained on ventilators for both >7 and >14 days met significantly more I-TRACH criteria than those requiring shorter durations of MV (1.7 ± 1.3 vs 2.8 ± 1.3 vs 3.8 ± 1.3 criteria, P < .001). I-TRACH performed better than all other models used to predict the duration of MV.

Conclusion: Similar to our previous retrospective study, these findings validate I-TRACH in determining the subsequent need for MV >7 and >14 days at the time of intubation.
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http://dx.doi.org/10.1177/0885066616679974DOI Listing
October 2018

Differential expression of extracellular matrix remodeling genes in rat model of hemorrhagic shock and resuscitation.

J Surg Res 2005 Feb;123(2):235-44

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Background: Matrix metalloproteinases (MMPs) and their specific physiological inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are thought to play an essential role in tissue repair, cell death and morphogenesis. We have previously discovered unexpected up-regulation of genes coding for multiple MMP/TIMP family members in a rat model of hemorrhagic shock and resuscitation. However, the effect of different resuscitation protocols at the level of protein expression and function remains unknown.

Materials And Methods: Male Sprague-Dawley rats (n = 50; 10/group) were subjected to a three-stage volume controlled hemorrhage and resuscitated as follows: 1) lactated Ringer's solution (LR), 3:1 volume of lost blood; 2) 7.5% hypertonic saline (HTS), 9.7 ml/kg; 3) plasma, 1:1 volume. Sham hemorrhage and sham resuscitation groups were used as controls. Expression of lung and spleen MMPs (-2, -7, -9, -10, -14, and -16), and TIMPs (-1, -2, and -3) was analyzed at transcriptional, functional and protein expression level using RT-PCR, ELISA, Western blotting, and gelatin zymography techniques.

Results: Spleen was affected more than lung by the resuscitation strategy and the largest number of changes was caused by HTS resuscitation. RT-PCR confirmed an increased levels of MMP-2, MMP-9, MMP-7, MMP-14, MMP-16, and TIMP-1, TIMP-2 in the spleen of HTS group compared to sham groups, whereas in lungs transcriptional levels of only TIMP-3 and TIMP-1 were significantly changed.

Conclusion: Expression of MMP and TIMP in lung and spleen following hemorrhage is modulated by the resuscitation strategy.
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http://dx.doi.org/10.1016/j.jss.2004.08.025DOI Listing
February 2005

The rate of induction of hypothermic arrest determines the outcome in a Swine model of lethal hemorrhage.

J Trauma 2004 Nov;57(5):961-9

Trauma Research and Readiness Institute for Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.

Background: Lethal injuries can be surgically repaired under asanguineous hypothermic condition (suspended animation) with excellent outcome. However, the optimal rate for the induction of hypothermic metabolic arrest following uncontrolled lethal hemorrhage (ULH) is unknown.

Methods: ULH was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 minutes later by laceration of the descending thoracic aorta. Through a left thoracotomy approach, total body hypothermic hyperkalemic metabolic arrest was induced by infusing organ preservation fluids into the aorta. Experimental groups were: normothermic controls (no cooling, NC), or hypothermia induced at a rate of 0.5 degrees C/min (slow, SC), 1 degrees C/min (medium, MC), or 2 degrees C/min (fast, FC). Vascular injuries were repaired during the 60 minutes of profound (10 degrees C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid exchange, and blood was infused for resuscitation during the re-warming (0.5 degrees C/ minute) period. The survivors were monitored for 6 weeks.

Results: The 6 week survival rates were 0% (NC), 37.5% (SC), 62.5% (MC), and 87.5% (FC) respectively (p < 0.05 MC&FC versus NC). All of the surviving hypothermic arrest animals were neurologically intact and displayed no long term organ dysfunction.

Conclusion: Hypothermic metabolic arrest can be used to maintain viability of key organs during repair of lethal injuries. Survival is influenced by the rate of cooling with the best outcome following rapid induction of hypothermia.
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http://dx.doi.org/10.1097/01.ta.0000149549.72389.3fDOI Listing
November 2004

Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin injury in Swine.

J Trauma 2004 May;56(5):974-83

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Background: Techniques for better hemorrhage control after injury could change outcome. We have previously shown that a zeolite mineral hemostatic agent (ZH) can control aggressive bleeding through adsorption of water, which is an exothermic process. Increasing the residual moisture content (RM) of ZH can theoretically decrease heat generation, but its effect on the hemostatic properties is unknown. We tested ZH with increasing RM against controls and other hemostatic agents in a swine model of battlefield injury.

Methods: A complex groin injury was created in 72 swine (37 +/- 0.8 kg). This included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 3 minutes, the animals were randomized to 1 of 10 groups: group 1, no dressing (ND); group 2, standard dressing (SD); group 3, SD + 3.5 oz ZH with 1% RM (1% ZH); group 4, SD + 3.5 oz ZH with 4% RM (4% ZH); group 5, SD + 2 oz ZH with 1% RM (1% ZH 2oz); group 6, SD + 3.5 oz ZH with 8% RM (8% ZH); group 7, SD + chitosan-based hemostat, HemCon (HC); group 8, SD + 3.5 oz nonzeolite mineral hemostat, Quick Relief (NZH); group 9, SD + bovine clotting factors-based hemostat, Fast Act (FA); and group 10, SD + 30 g of starch-based hemostat, TraumaDex (TDex). Resuscitation (500 mL of Hespan over 30 minutes) was started 15 minutes after injury and hemodynamic monitoring was performed for 180 minutes. Primary endpoints were survival for 180 minutes and blood loss. In addition, maximum wound temperatures were recorded, and histologic damage to artery, vein, nerve, and muscle was documented.

Results: Use of 1% ZH decreased blood loss and reduced mortality to 0% (p < 0.05). Increasing the RM adversely affected efficacy without any significant decrease in wound temperatures. Minimal histologic tissue damage was seen with ZH independent of the percentage of RM.

Conclusion: The use of zeolite hemostatic agent (1% residual moisture, 3.5 oz) can control hemorrhage and dramatically reduce mortality from a lethal groin wound.
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http://dx.doi.org/10.1097/01.ta.0000127763.90890.31DOI Listing
May 2004

A portable handpump is effective in the evacuation of hemothorax in a swine model of penetrating chest injury.

J Trauma 2003 Nov;55(5):864-8

Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.

Background: Standard pleural evacuation devices are not practical for use on the battlefield. A small, portable, easy-to-use handpump (HP) that does not require continuous suction for treating hemopneumothorax would offer a major logistical advantage. In addition, using endotracheal tubes instead of regular pleural tubes would help minimize supplies carried on the battlefield. A swine model of penetrating chest injury was designed to test this concept. Our hypothesis was that an HP would be as effective as the standard of care for the evacuation of a large hemopneumothorax.

Methods: A 2-cm lung laceration was created in 18 Yorkshire swine (35-51 kg) under inhaled anesthesia and 1.4 L of blood was infused into the pleural space (200 mL every 15 minutes). Fluid resuscitation (2,000 mL of 0.9% saline) was started 15 minutes after injury, and animals were randomized into one of three groups: group 1, 36-Fr Argyle pleural tube and Pleur-Evac chest drainage unit with 20-cm H2O suction (control); group 2, 36-Fr pleural tube attached to the HP; and group 3, a No. 8 endotracheal tube in the pleural space attached to the HP. After 120 minutes, a thoracotomy was performed to determine the amount of residual blood in the pleural space.

Results: Effectiveness of the three methods as a percentage of total blood (evacuated and retained) removed was measured over 2 hours. The handpump (group 2) performed better than the standard of care (group 1) at numerous time points and evacuated significantly (p < 0.05) more blood at the end of the experiment.

Conclusion: Using the handpump with a pleural tube was more effective than the standard of care in treating traumatic hemothorax. The use of an endotracheal instead of a conventional pleural tube had no adverse impact on efficacy of the pump in evacuating blood from the chest cavity.
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http://dx.doi.org/10.1097/01.TA.0000090036.55859.54DOI Listing
November 2003

Ketone and pyruvate Ringer's solutions decrease pulmonary apoptosis in a rat model of severe hemorrhagic shock and resuscitation.

Surgery 2003 Aug;134(2):267-74

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Background: Resuscitation fluids containing beta-hydroxybutyrate (BHB) have been shown to decrease cellular injury after hemorrhagic shock and resuscitation through an unknown mechanism. We tested whether this effect was related to BHB-induced metabolic modulations.

Methods: Male Sprague Dawley rats (n=30) were subjected to volume-controlled hemorrhage (27 mL/kg during 10 minutes followed by 75 minutes of shock during which another 8 mL/kg of blood was withdrawn). Experimental groups included the following: (1) sham, (2) no resuscitation (NR), (3) racemic lactated Ringer's (DL-LR) solution, (4) LR containing L-isomer only (L-LR), (5) ketone Ringer's solution with lactate substituted by BHB (KR), and (6) pyruvate Ringer's solution with lactate substituted by pyruvate (PR). The resuscitation fluids were infused during 45 minutes simultaneously with additional hemorrhage of 8 mL/kg. Hemodynamic and physiologic parameters and the plasma levels of BHB were serially measured. The animals were killed 2 hours after resuscitation, and tissues were frozen instantaneously for cellular adenylate extraction and adenosine triphosphate (ATP) and adenosine diphosphate analysis. Pulmonary apoptosis was studied using Western blotting, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Expression of enzymes involved in ketogenesis and ketolysis was analyzed by reverse transcriptase-polymerase chain reaction.

Results: NR and resuscitation with DL-LR increased the expression of apoptotic markers, whereas resuscitation with KR and PR significantly decreased the expression of apoptotic markers in rat lungs. Resuscitation with KR was followed by a profound increase in plasma BHB levels; however, the expression levels of ketolytic enzymes were essentially unaffected. KR infusion did not induce significant improvements in tissue ATP levels.

Conclusions: Resuscitation with KR and PR protects against pulmonary apoptosis without improving tissue ATP content. Therefore, metabolic modulation is unlikely to be the major mechanism by which BHB exerts its protective effects during reperfusion.
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http://dx.doi.org/10.1067/msy.2003.245DOI Listing
August 2003

Comparative analysis of hemostatic agents in a swine model of lethal groin injury.

J Trauma 2003 Jun;54(6):1077-82

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.

Background: Techniques for better hemorrhage control after injury could change outcome. A large-animal model of lethal, uncontrolled hemorrhage was developed to test whether the use of various hemostatic agents would decrease bleeding and improve early survival.

Methods: A complex groin injury was created in 30 Yorkshire swine (42-55 kg) to produce uncontrolled hemorrhage. This injury included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 5 minutes, the animals were randomized to (n = 6 animals per group) no dressing (ND), standard dressing (SD), SD and Rapid Deployment Hemostat (RDH) bandage, SD and QuikClot hemostatic agent (QC), or SD and TraumaDEX (TDEX). Limited volume 0.9% saline (1,000 mL over 30 minutes) resuscitation was started 30 minutes after injury. We measured blood loss, early mortality (180 minutes), and physiologic markers of hemorrhagic shock (e.g., cardiac output, blood pressure, hemoglobin, metabolic acidosis).

Results: Application of wound dressing decreased mortality in all groups compared with the ND group (83% mortality). However, this difference was significant (p < 0.05) only for the QuikClot hemostatic agent (0% mortality). Before the application of dressing (first 5 minutes), there were no differences in blood loss between the groups. After application of dressings, the QC group had the lowest blood loss (4.4 +/- 1.4 mL/kg).

Conclusion: Of the hemostatic agents tested, QuikClot improved survival and decreased bleeding in a swine model of lethal vascular and soft tissue injury.
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http://dx.doi.org/10.1097/01.TA.0000068258.99048.70DOI Listing
June 2003