Biomedical subjects

Peter Rhee

Publications and source records attributed to Peter Rhee.

14 recordsLinked to original sources

PubMed2003

High success with nonoperative management of blunt hepatic trauma: the liver is a sturdy organ.

HYPOTHESIS: Nonoperative management of liver injuries (NOMLI) is highly successful and rarely leads to adverse events. DESIGN: Prospective observational study. SETTING: High-volume academic level I trauma center. PATIENTS: For 26 months, 78 consecutive unselected patients with liver injuries were followed up prospectively. In the absence of hemodynamic instability or signs of hollow visceral trauma, NOMLI was offered irrespective of the magnitude of the liver injury. Main Outcome Measure Failure of NOMLI, defined as a laparotomy after an initial decision to treat the patient nonoperatively. RESULTS: Of the 78 patients, 23 (29%) were operated on immediately, but only 12 (15%) for bleeding from the liver. All 12 patients required packing in addition to other maneuvers (hepatorrhaphy [n = 8], resection [n = 4], and liver isolation [n = 1]). Of the remaining 55 patients selected for NOMLI, the method failed in 8 for reasons unrelated to the liver injury: 2 underwent a splenectomy, 1 underwent a nephrectomy, 1 had a small-bowel repair, 1 underwent abdominal decompression for abdominal compartment syndrome, and 3 underwent a nontherapeutic laparotomy. The success rate of NOMLI was 85% (47 of 55 patients), but the liver-specific success rate was 100%. Compared with those in whom NOMLI was successful, patients in whom it failed had a higher Injury Severity Score and underwent more blood transfusions, but they had similar liver injury grades. In total, 66 (85%) of liver injuries did not bleed significantly. No adverse events were attributed to NOMLI. CONCLUSIONS: Nonoperative management of liver injuries is safe and effective regardless of the grade of liver injury. Failure of NOMLI is caused by associated abdominal injuries and not the liver. Fluid and blood requirements, the degree of injury severity, and the presence of other abdominal organ injuries may help predict failure.

Abdominal Injuries↗

PubMed2003

cDNA profiling in leukocytes exposed to hypertonic resuscitation fluids.

BACKGROUND: Resuscitative fluids induce distinctive changes in leukocyte functions: incubation with colloid Dextran increases production of reactive oxygen species and adhesion, whereas exposure to hypertonic saline (HTS) inhibits "oxidative burst" and phagocytosis. In hypertonic saline Dextran (HTD), the hypertonic component determines the leukocyte functional behavior and subsequently activation response. We investigated whether leukocyte gene expression is analogously affected. METHODS: Whole blood from eight volunteers was diluted and incubated for 30 min at 37(o)C in 6.0% Dextran-70, 7.5% HTS, and 7.5% HTD. Total leukocyte RNA was extracted and used to synthesize biotinylated cDNA probes. Each probe was individually hybridized to a cDNA array to simultaneously measure the expression of 23 genes involved in inflammation, cell migration, and apoptosis. RESULTS: Leukocytes incubated with Dextran-70 demonstrated greater than a 6-fold (p < 0.05) increase in the expression of interleukin-8, growth-regulated oncogenes alpha and beta, L-selectin, superoxide dismutase, tumor necrosis factor-alpha (TNF-alpha), and mitogen-activated protein kinase 3. The expression profile induced by HTS was not significantly different from that of unstimulated blood, except for prominent induction of only three genes. HTD attenuated the expression of Dextran-70 upregulated genes, although the level of their expression was higher than in HTS-treated leukocytes. CONCLUSIONS: Hypertonic resuscitation fluids diminish the expression of immune activation-associated genes. Hypertonic component of HTD determines the leukocyte gene expression profile.

Adult↗

PubMed2003

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

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.

3-Hydroxybutyric Acid↗

PubMed2003

Battlefield casualties treated at Camp Rhino, Afghanistan: lessons learned.

BACKGROUND: Operation Enduring Freedom is an effort to combat terrorism after an attack on the United States. The first large-scale troop movement (> 1,300) was made by the U.S. Marines into the country of Afghanistan by establishing Camp Rhino. METHODS: Data were entered into a personal computer at Camp Rhino, using combat casualty collecting software. RESULTS: Surgical support at Camp Rhino consisted of two surgical teams (12 personnel each), who set up two operating tables in one tent. During the 6-week period, a total of 46 casualties were treated, and all were a result of blast or blunt injury. One casualty required immediate surgery, two required thoracostomy tube, and the remainder received fracture stabilization or wound care before being transported out of Afghanistan. The casualties received 6 major surgical procedures and 11 minor procedures, which included fracture fixations. There was one killed in action and one expectant patient. The major problem faced was long delay in access to initial surgical care, which was more than 5 hours and 2 hours for two of the casualties. CONCLUSION: Smaller, more mobile surgical teams will be needed more frequently in future military operations because of inability to set up current larger surgical facilities, and major problems will include long transport times. Future improvements to the system should emphasize casualty evacuation, en-route care, and joint operations planning between services.

Afghanistan↗

PubMed2003

Human polymorphonuclear cell death after exposure to resuscitation fluids in vitro: apoptosis versus necrosis.

BACKGROUND: Resuscitation fluids can have variable effects on key functions of circulating polymorphonuclear neutrophils (PMNs) such as oxidative burst, chemotaxis, and bacterial killing. We hypothesized that choice of resuscitation fluids will also affect the rate of PMN apoptosis. To test this, we studied cellular death (apoptosis and necrosis) in human PMNs after brief exposure to different hypertonic and isotonic fluids. METHODS: Blood from 12 volunteers was incubated for 1 hour at 37 degrees C in normal saline, 6.0% dextran-70, 7.5% hypertonic saline, and 7.5% hypertonic saline with 6% dextran-70. Isolated PMNs were double labeled with fluorescein-Annexin V and propidium iodide, and apoptosis and necrosis were measured using flow cytometry. Caspase activation was also detected with flow cytometry using pan-caspase inhibitor (carbobenzoxy-valyl-alanyl-aspartyl-fluoromethylketone) in non-isolated whole blood samples to determine apoptosis. Finally, cDNA macroarrays were used to evaluate the expression of 23 genes involved in the regulation of cell cycling and apoptosis. RESULTS: Exposure to hypertonic fluids (hypertonic saline and 7.5% hypertonic saline with 6% dextran-70) significantly (p < 0.05) increased necrosis in isolated PMNs. In whole blood samples, PMNs exposed to dextran demonstrated significant apoptosis as evidenced by increased caspase activation. Dextran was the only fluid that affected leukocyte gene expression, inducing significant up-regulation of Rb gene transcription. CONCLUSION: Hypertonic fluids and dextran decrease human polymorphonuclear cell survival through necrotic and apoptotic pathways, respectively.

Apoptosis↗

PubMed2003

Searching for the optimal resuscitation method: recommendations for the initial fluid resuscitation of combat casualties.

Resuscitation can exacerbate cellular injury caused by hemorrhagic shock, and the type of fluid used for resuscitation may play an important role in this injury. Unlike some factors in the treatment of combat casualty, the method of resuscitation is under our control. The prevention of cellular injury through wiser resuscitation strategies would be more advantageous than attempting complex immunomodulation after the damage has already occurred. This article summarizes data from a number of studies to illustrate the differential effects of commonly used resuscitation fluids on cellular injury. Our findings show that resuscitation with hypotonic/isotonic crystalloids, including lactated Ringer's (LR) solution, and artificial colloid solutions, elicit severe immune activation and an up-regulation of cellular injury markers. This effect is not seen with plasma, natural colloids (albumin), and fresh whole blood. Hypertonic fluids cause suppression of neutrophil activation and a milder increase in the expression of cell injury markers compared with isotonic fluids. The effect of various resuscitation fluids on core cellular functions such as gene regulation is also summarized in this article. Finally, because of the uniqueness of combat care, a set of new recommendations for initial fluid resuscitation of combat casualties is proposed.

Animals↗

PubMed2003

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

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.

Animals↗

PubMed2003

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

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.

Animals↗

PubMed2003

Adolescent assault injury: risk and protective factors and locations of contact for intervention.

BACKGROUND: Violence is a large contributor to morbidity and mortality among adolescents. Most studies assessing markers for violent injury are cross-sectional. To guide intervention, we conducted a case-control study to explore factors associated with assault injury and locations to reach at-risk adolescents. OBJECTIVE: 1) To assess risk and protective factors for adolescent assault injury compared with 2 control groups of youth with unintentional injuries and noninjury complaints presenting to the emergency department and 2) to assess locations of contact with assault-injured youth for prevention programs. METHODS: Face-to-face and phone interviews were conducted with systematic samples of youth aged 12 to 19 years presenting to the emergency department with assault injury, unintentional injury, and noninjury complaints. Youth with intentional injuries were matched to youth in the 2 control groups on age +/-1 year, gender, race, and residency. RESULTS: One hundred forty-seven 147 assault-injured youth completed interviews. One hundred thirty-three assault-injured youth were matched to 133 unintentionally injured and 133 noninjured youth presenting to the emergency department. Compared with the 2 control groups, assault-injured youth were more likely to have had more fights in the past year (odds ratio [OR]: 3.91; 95% confidence interval [CI]: 2.02, 7.58; OR: 4.00; 95% CI: 2.23, 7.18) and fights requiring medical treatment (OR: 35.49; 95% CI: 8.71, 144.68; OR: 80.00; 95% CI: 11.13, 574.80). Eighty percent of assault-injured youth had been in 1 or more fights in the last 12 months compared with 55% and 46% in unintentional and noninjured controls, respectively. Assault-injured youth were more likely to have had previous weapon injuries (OR: 9.50; 95% CI: 3.39, 26.6; OR: 8.50; 95% CI: 3.02, 23.95) and have seen someone shot (OR: 2.00; 95% CI 1.12, 3.58; OR: 2.00; 95% CI: 1.12, 3.58). Eighty-six percent of assault-injured youth had a regular health care provider with 82% reporting a visit within the last year. There were no differences between cases and controls with regard to physician contact, extracurricular activity involvement, school or church attendance, police contact, weapon access or weapon-carrying, or witnessing nonweapon-related violence. CONCLUSIONS: Fighting was common among all groups. Assault-injured youth were more likely to have had previous weapon injuries and were high-risk for future injury. Past fights, past fight injuries, and seeing someone else shot were markers associated with assault injury. Health providers do have access to at-risk teens for clinical risk assessment and intervention.

Accidents↗

PubMed2003

Intubation after cervical spinal cord injury: to be done selectively or routinely?

Patients with cervical spinal cord injuries (CSCIs) often develop acute respiratory failure and require intubation. It is unknown if intubation should be offered preemptively in all CSCI patients or selectively based on signs of acute respiratory failure. The purpose of this study was to evaluate the role of routine early intubation in CSCI patients. The medical records of 68 patients with CSCI were reviewed. Univariate and multivariate analyses were used to identify independent risk factors for the need of intubation. Statistical significance was considered at P < 0.05. Fifty patients (74%) required intubation and 27 (40%) developed pneumonia. Of patients with CSCI above C5, 87.5 per cent required intubation compared with 61 per cent of patients with CSCI at C5-C8 (P = 0.026). Similarly, of patients with complete quadriplegia, 90 per cent required intubation compared to 48.5 per cent of patients with incomplete quadriplegia or paraplegia (P < 0.001). Of 31 patients not presenting with overt signs of acute respiratory failure on admission, 13 (42%) decompensated later and were eventually intubated up to 53 hours after admission. Six of these 13 patients had emergent intubation due to acute desaturation and developed pulmonary complications associated with emergent intubation. There were 3 independent risk factors for the need of intubation: Injury Severity Score > 16, CSCI higher than C5, and complete quadriplegia. The combination of the 2 latter risk factors resulted in intubation in 21 of 22 patients (95%). The majority of patients with CSCI require intubation. In patients with CSCI above C5 and complete quadriplegia, intubation should be offered routinely and early because delays may cause preventable morbidity.

Adult↗

PubMed2002

cDNA array analysis of gene expression following hemorrhagic shock and resuscitation in rats.

UNLABELLED: The aim of this study was to characterize gene expression following hemorrhagic shock and resuscitation with emphasis on the differences between various resuscitation strategies. METHODS: Male Sprague Dawley rats (n = 25; 5/group) were subjected to a three stage hemorrhage and resuscitated as follows: (1) sham hemorrhage; (2) sham resuscitation; (3) lactated Ringer's solution (LR), 3:1 volume; (4) 7.5% hypertonic saline (HTS) 9.7 ml/kg; (5) plasma, 1:1 volume. Liver, spleen, lung and muscle were collected 3 h post resuscitation and cDNA array analysis was performed on the total RNA. RESULTS: Expression of 1,176 genes was analyzed. Following resuscitation, 82 of the genes studied (7%) displayed an altered expression of at least 2-fold compared to the sham hemorrhage group. Depending on organ system under study and resuscitation conditions, expression of these 82 genes was down- or up-regulated, bringing the total number of expression alterations to 167. Largest number of organ-specific changes in gene expression was noted in liver (63/167), followed by lung (57), muscle (25), and spleen (22). Most of the resuscitation strategy specific changes were caused by plasma resuscitation (68/167), followed by LR (51), and HTS (48). In every organ studied, gene expression profile was dependent upon the fluid used for resuscitation. CONCLUSION: Cellular response to hemorrhagic shock, even at the level of gene expression, is dependent on the resuscitation strategy. We have discovered altered expression of genes not previously implicated in the physiology of hemorrhagic shock and resuscitation. Gene array technology provides a rapid and efficient means of dissecting the complex genetic regulation of cellular response to shock.

Animals↗

PubMed2002

Learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination.

BACKGROUND: Induced asanguineous hypothermic metabolic arrest (suspended animation) could provide valuable time to repair major vascular injuries if safely induced in patients with trauma. We report a novel method of doing this in a swine model of uncontrolled lethal hemorrhage (ULH) that resulted in preservation of learning ability and memory. METHODS: Yorkshire swine (100 to 125 lb) underwent ULH before rapid intra-aortic infusion of a hypothermic (4 degrees C), hyperkalemic (70 mEq/L) organ preservation solution by a left thoracotomy. Cooling continued until core temperature reached 10 degrees C, and this was maintained for 60 minutes using low-flow cardiopulmonary bypass. Vascular injuries were repaired during this state of suspended animation, which was then reversed, and the animals were observed for 6 weeks. Cognitive functions were tested by training animals to retrieve food from color-coded boxes. Postoperatively, the ability to remember this task and a 75-point objective neurologic scale were used to test neurologic function. In experiment I, ULH was caused by lacerating thoracic aorta (n = 9). Five preoperatively untrained animals were trained to perform the task and compared with control animals (n = 15), and 4 preoperatively trained animals were tested for memory retention postoperatively. In experiment II, ULH was induced by creating an iliac artery and vein injury (n = 15). Animals were kept in shock for 15, 30, and 60 minutes before the induction of hypothermia. RESULTS: In experiment I, surviving animals (7/9) were neurologically intact, and their capacity to learn new skills was no different than for control animals. All pretrained animals demonstrated complete memory retention. In experiment II, survival with 15, 30, and 60 minutes of shock were 80%, 60%, and 80%, respectively. All animals (except 1) in the 60-minute group were neurologically intact and displayed normal learning capacity. CONCLUSIONS: Induction of hypothermic metabolic arrest (by thoracotomy) for repair of complex traumatic injuries is feasible with preservation of normal neurologic function, even after extended periods of shock from an intra-abdominal source of uncontrolled hemorrhage.

Animals↗

PubMed2002

Hypertonic saline: intraosseous infusion causes myonecrosis in a dehydrated swine model of uncontrolled hemorrhagic shock.

BACKGROUND: The Institute of Medicine has recommended intraosseous (IO) infusion of 7.5% hypertonic saline (HTS) for combat casualties in shock. We tested the safety and efficacy of this recommendation in a long-term survival model of uncontrolled hemorrhagic shock using dehydrated swine. METHODS: Fourteen dehydrated Yorkshire swine had placement of a 12G needle in the right anterior tibia under isoflurane anesthesia. Uncontrolled hemorrhage was induced via left iliac artery and vein injury. Animals were kept in shock for 2 hours and then resuscitated over 2 hours with 5 mL/kg of 7.5% HTS given either as 10 small boluses (group I, n = 4) or two large boluses (group II, n = 6) to compare the physiologic response and blood loss. Control animals (group III, n = 4) received an equal volume of 0.9% saline IO and additional intravenous saline to equalize the salt load in all groups. RESULTS: The three groups had similar physiologic responses, with no increase in blood loss following HTS resuscitation. However, between the second and fifth postresuscitation days, the 7.5% HTS resuscitated animals developed soft tissue necrosis or bone marrow necrosis of the right hind leg (group I, 100%; group II, 66.6%; group III, 0%). CONCLUSION: HTS resuscitation effectively restored hemodynamic stability in dehydrated swine without increased bleeding from an uncontrolled vascular injury. However, IO infusion of HTS in this model was associated with a very high rate of local complications. Further investigations should be undertaken before IO use of 7.5% HTS in humans.

Animals↗

PubMed2002

Comparison of the effects of a 50% exchange-transfusion with albumin, hetastarch, and modified hemoglobin solutions.

We compared the hemodynamic effects of replacing 50% of the blood volume of anesthetized rats with an equal volume of five solutions: human serum albumin (HSA), hetastarch, unmodified hemoglobin, diaspirin-crosslinked hemoglobin, and o-raffinose-crosslinked hemgolobin. Control rats were exchange-transfused with their own blood. HSA and hetastarch caused a severe reduction in systemic vascular resistance (SVR), hypotension, and acute renal failure immediately after the exchange-transfusion. Unmodified and diaspirin-crosslinked hemoglobins caused comparable and severe increases in SVR, whereas vasoconstriction induced by o-raffinose-crosslinked hemoglobin was minimal. The increased SVR induced by all hemoglobin solutions resolved over a 2-day period as the hemoglobin was cleared from plasma. Body weight was monitored for 5 days after the exchange transfusion as a measure of the relative long-term efficacy of the exchange solutions tested and increased substantially in control rats (that received blood). Rats that received both crosslinked hemoglobin solutions gained a comparable amount of weight as the control group. By contrast rats that received HSA, hetastarch and unmodified hemoglobin failed to gain weight or lost weight over the same period. In summary: i) HSA and hetastarch are relatively ineffective as resuscitative fluids when administered after the loss of a large volume of blood; ii) diaspirin-crosslinked hemoglobin causes severe vasoconstriction, comparable in intensity to that induced by unmodified hemoglobin; iii) o-raffinose-crosslinked hemoglobin induces minimal vasoconstriction; iv) the vasoactive effects of all hemoglobin solutions are reversible. We conclude, that of all solutions tested, both the short- and long-term effects of an exchange-transfusion with whole blood are most closely reproduced by an exchange with o-raffinose-crosslinked hemoglobin.

Animals↗