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Biomedical subjects

Peter Rhee

Publications and source records attributed to Peter Rhee.

At least 73 records · Page 4Linked to original sources

Pedestrians injured by automobiles: relationship of age to injury type and severity.

BACKGROUND: There is little research on the effect of age on the nature and severity of injuries to pedestrians struck by automobiles. STUDY DESIGN: Trauma registry study included all auto versus pedestrian trauma admissions of pedestrians injured by automobiles at an academic Level I trauma center over 10 years and 4 months. Injury Severity Score, severe body area (head, chest, abdomen, extremities) trauma with Abbreviated Injury Score >3, specific organ injuries, and mortality were calculated according to age groups (< or =14 years, 15 to 55 years, 56 to 65 years, >65 years). RESULTS: During the study period 5,838 admissions were reviewed. There were 1,136 patients (19.4%) 14 years old or less, 3,741 (64.1%) who were 15 to 55 years, 420 (7.2%) 56 to 65 years, and 541 (9.3%) older than 65 years. Overall mortality was 7.7% and ranged from 3.2% in the age group 14 years or less to 25.1% in patients over 65 years. The incidences of severe trauma (Injury Severity Score >15) in the four age groups were 11.2%, 18.7%, 23.6%, and 36.8%, respectively. The incidences of critical trauma (Injury Severity Score >30) were 2.3%, 3.9%, 5.7%, and 13.9%, respectively. The incidence of severe head and chest trauma (Abbreviated Injury Score >3) increased with age. The incidence of solid organ and hollow viscus injuries was similar in all age groups. Spinal injuries increased significantly with age and ranged from 0.4% in the pediatric group to 8.5% in the elderly group. Pelvic and tibial fractures were significantly more common in adults; femur fractures were significantly more common in the pediatric group. CONCLUSIONS: Age plays an important role in the anatomic distribution and severity of injuries and survival outcomes after pedestrian injuries.

Abdominal Injuries↗

Liver cirrhosis in patients undergoing laparotomy for trauma: effect on outcomes.

BACKGROUND: There is little published work on the effect of cirrhosis on outcomes in trauma patients undergoing laparotomy. The aim of this study was to evaluate the risk of death or serious complications in cirrhotic trauma patients undergoing laparotomy as compared with that in a similar group of patients without cirrhosis. STUDY DESIGN: During a 12-year period, there were 46 patients with the diagnosis of liver cirrhosis made during laparotomy for trauma. Each patient was matched with two noncirrhotic controls on the basis of 7 criteria: age (>55, </=55 years), gender, mechanism of injury (blunt, penetrating), Injury Severity Score (</=15, 16-25, >25), head Abbreviated Injury Score (<3, >/=3), chest Abbreviated Injury Score (<3, >/=3), and abdominal Abbreviated Injury Score (<3, >/=3). Six cirrhotic patients were excluded because matching was not possible. The remaining 40 patients were matched with 80 noncirrhotic control patients selected from a pool of 4,771 patients who had trauma laparotomies. Outcomes included mortality, ARDS, pneumonia, renal failure, abdominal sepsis, disseminated intravascular coagulopathy, ICU and hospital stay, and hospital charges. Outcomes between the two study groups were compared with conditional logistic analysis. Hazard ratio (95% CI) and adjusted p value with the stepdown Bonferroni method were derived. RESULTS: The overall mortality in the cirrhotic group was significantly higher than that in the matched noncirrhotic group (45% versus 24%, hazard ratio: 7.60 [2.00, 28.94], p = 0.021). Mortality in patients with Injury Severity Score </=15 was 29% in the cirrhotic group and 5% in the noncirrhotic group (p = 0.013) and in patients with Injury Severity Score 16-25, mortality was 56% and 11%, respectively (p = 0.024). The incidence of any of the predetermined complications was 45% in the cirrhotic group and 23% in the noncirrhotic group (p = 0.110). The mean surgical ICU stay was 11.5 days and 6.6 days, respectively (p = 0.037), and the mean hospital charges were $141,210 and $72,884, respectively (p = 0.031). CONCLUSIONS: Cirrhotic trauma patients undergoing laparotomy are at high risk of serious complications and death, even after fairly minor injuries. This group of patients should be admitted to the ICU for close monitoring and aggressive management irrespective of the severity of injuries.

Female↗

Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock.

UNLABELLED: Activated neutrophils play a pivotal role in resuscitation injury. The strategies used for resuscitation (types of fluids and methods of administration) can affect the degree of neutrophil activation. The aim of this study was to test the commonly available resuscitation fluids in a large animal model of hemorrhagic shock to determine the strategy associated with the least degree of neutrophil activation. METHODS: Female swine (n=63, weight 45-60 kg) were anesthetized using isoflurane and catheters were placed for hemodynamic monitoring. After 120 min, they were subjected to a volume controlled hemorrhage (28 ml/kg) over 15 min, kept in shock for 60 min, and then resuscitated. The resuscitation groups were as follows: (1) anesthesia only (n=5); (2) hemorrhage, sham resuscitation (n=5); (3) LR-fast rate 3x blood loss (n=6); (4) LR slow rate-3x blood loss (n=6); (5) LR low volume-1x blood loss (n=6); (6) Dextran 40-1x blood loss (n=6); (7) 6% hetastarch-1x blood loss (n=6); (8) 5% albumin-1x blood loss (n=6); (9) 25% albumin-1/5x blood loss (n=6); (10) whole blood resuscitation-1x blood loss (n=6); (11) 7.5% hypertonic saline (HTS)-0.3x blood loss (n=5). Resuscitation fluids were infused over 1 h in all groups except group 4 (LR slow rate, which was over 3 h). Animals were observed for 180 min following the resuscitation period. Neutrophil oxidative burst activity was determined in whole blood using flow cytometery. RESULTS: Animals resuscitated with dextran and hetastarch showed significantly (P<0.05) higher neutrophil burst activity. Resuscitation with LR also caused neutrophil activation (P<0.05), and the highest degree of activation was seen when a large volume of LR was given at a fast rate (group 8). However, all LR infusion protocols were associated with significant neutrophil activation compared with anesthesia (group 1) or sham resuscitation (group 2). No significant activation was seen in the animals resuscitated with albumin or fresh whole blood. CONCLUSION: Artificial colloids and LR (independent of rate or volume of infusion) caused significant neutrophil activation, which was not seen with albumin and whole blood resuscitation. These findings suggest that the type of resuscitation fluid and method of infusion can influence neutrophil function.

Albumins↗

Traumatic injuries to the portal vein: case study.

BACKGROUND: Injuries to the portal vein are rare but devastating. Contemporary studies have debated the most effective management for this injury. The purpose of this case study was to provide an update on portal vein injury and add information regarding its management. METHODS: A retrospective review investigated the 10-year experience with portal vein injury in a level 1 trauma center. RESULTS: Of the 18,900 trauma patients (0.08%) evaluated during a 10-year period, 15 sustained injuries to the portal vein. All the injuries resulted from penetrating trauma, and the overall survival rate was 60% (9 of the 15 patients). Four patients died of exsanguination and two patients died later as a result of multisystem organ failure. Postoperative complications were common. Sepsis and wound infection were the most common postoperative complications, occurring in seven (78%) of the nine survivors. All the patients had associated nonvascular injuries, whereas 9 (60%) of the 15 had associated vascular injuries. Associated injuries to the other structures in the portal triad occurred in 7 (47%) of the 15 patients, and 5 (71%) of these patients survived. Survival rates by procedure were 86% for venorrhaphy and 67% for ligation. CONCLUSIONS: Injuries to the portal vein are rare. In this study, exsanguination was the main cause of death. The key to a favorable outcome is prompt control of hemorrhage with an early decision to proceed with either venorrhaphy or ligation. Ligation can be effective for the management of hemodynamically unstable patients.

Adolescent↗

Can we rely on computed tomographic scanning to diagnose pulmonary embolism in critically ill surgical patients?

BACKGROUND: Spiral computed tomographic pulmonary angiography (CTPA) is gaining an increasing role in pulmonary embolism (PE) diagnosis because it is more convenient and less invasive than conventional pulmonary angiography (PA). Encouraging reports on the reliability of CTPA for medical patients have prompted widespread use despite the fact that its value in critically ill surgical patients has been inadequately explored. Hemodynamic and respiratory issues of critical illness may interfere with CTPA's diagnostic accuracy. The objective of this study was to compare CTPA with PA for the diagnosis of PE in critically ill surgical patients. METHODS: Over 30 months (August 1999-February 2002), 37 critically ill surgical patients (28 trauma and 9 non-trauma patients) wiith clinical suspicion of PE were enrolled prospectively. CTPA and PA were independently interpreted by four radiologists (two for each test) blinded to each other's interpretation. Clinical suspicion for PE was classified as high, intermediate,or low on the basis of predetermined criteria. PA was considered as the standard of reference for the diagnosis of PE. RESULTS: PE was found in 15 (40%) patients by: central PE in 8 and peripheral PE in 7. CTPA and PA findings were different in 11 patients (30%): CTPA was false-negative in 9 patients and false-positive in 2. Its sensitivity and specificity were PE 50% and 100%, respectively, for central PE; 28% and 93% for peripheral PE; and 40% and 91% for all PE. There were no differences in risk factors or clinical characteristics between patients with and without PE. The level of clinical suspicion was identical in the two groups. The independent reviewers disagreed on CTPA or PA interpretations in 11% and 16% of the readings, respectively. CONCLUSION: PA remains the "gold standard" for diagnosis of PE in critically ill surgical patients. CTPA should be explored further before being universally accepted. Clinical criteria are unreliable for detecting PE in this population and therefore a high index of suspicion should be maintained.

Adolescent↗

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

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.

Adsorption↗

Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference?

BACKGROUND: The combination of bicarbonate and mannitol (BIC/MAN) is commonly used to prevent renal failure (RF) in patients with rhabdomyolysis despite the absence of sufficient evidence validating its use. The purpose of this study was to determine whether BIC/ MAN is effective in preventing RF in patients with rhabdomyolysis caused by trauma. METHODS: This study was a review of all adult trauma intensive care unit (ICU) admissions over 5 years (January 1997-September 2002). Creatine kinase (CK) levels were checked daily (abnormal,>520 U/L). RF was defined as a creatinine greater than 2.0 mg/dL. Patients received BIC/MAN on the basis of the surgeon's discretion. RESULTS: Among 2,083 trauma ICU admissions, 85% had abnormal CK levels. Overall, RF occurred in 10% of trauma ICU patients. A CK level of 5,000 U/L was the lowest abnormal level associated with RF; 74 of 382 (19%) patients with CK greater than 5,000 U/L developed RF as compared with 143 of 1,701 (8%) patients with CK less than 5,000 U/L (p < 0.0001). Among patients with CK greater than 5,000 U/L, there was no difference in the rates of RF, dialysis, or mortality between those who received BIC/MAN and those who did not. Subanalysis of groups with various levels of CK still failed to show any benefit of BIC/MAN. CONCLUSION: Abnormal CK levels are common among critically injured patients, and a CK level greater than 5,000 U/L is associated with RF. BIC/MAN does not prevent RF, dialysis, or mortality in patients with creatine kinase levels greater than 5,000 U/L. The standard of administering BIC/MAN to patients with post-traumatic rhabdomyolysis should be reevaluated.

Acute Kidney Injury↗

D-lactate increases pulmonary apoptosis by restricting phosphorylation of bad and eNOS in a rat model of hemorrhagic shock.

UNLABELLED: Resuscitation with racemic lactated Ringer's solution (containing equal amounts of D and L isomers of lactate) has been shown to induce pulmonary apoptosis. Substitution of DL-isomer lactate with ketone bodies (beta-hydroxybutyrate, BHB), sodium pyruvate, or L-isomer of lactate decrease this injury without changing the energy status of the tissues or the expression of apoptotic genes. These modified solutions however alter the function of apoptotic proteins through an unknown mechanism. We postulated that DL-LR induces apoptosis by restricting the phosphorylation of key apoptotic proteins. METHODS: Male Sprague Dawley rats (n = 30, 5/group) were subjected to a three stage, volume-controlled hemorrhage and randomized to the following groups. 1) No hemorrhage (Sham); 2) Hemorrhage and no resuscitation (NR); 3) Resuscitation with 3x shed blood volume of racemic LR (DL-LR); 4) Resuscitation with 3x shed blood volume of LR containing only the L-isomer of lactate (L-LR); 5) Resuscitation with 3s shed blood volume of pyruvate Ringer's (PR); 6) Resuscitation with 3s shed blood volume of ketone Ringer's (KR). The modified Ringer's solutions were identical to racemic LR except for equimolar substitution of DL-lactate for L-lactate, pyruvate and BHB respectively. Lung tissue was obtained 2 hours later and subjected to Western Blotting. The levels of Akt, Bad, and eNOS (total and phosphorylated) proteins were measured. Finally, the expression of gene coding for protein 14-3-3 was measured using RT-PCR. RESULTS: Resuscitation with DL-LR caused a significant (p < 0.05) increase in the total Bad and a decrease in phosphorylated Bad protein expression in the lung. It also caused an increase in the phosphorylated Akt levels and a decrease in gene coding for protein 14-3-3. These changes were consistent with signaling imbalances that favor apoptosis. Modified LR solutions, on the other hand, did not cause these alterations. Phosphorylation pattern of eNOS supported the involvement of PI3K/Akt pathway in this process. CONCLUSION: Racemic lactate plays a role in the induction of pulmonary apoptosis by restricting phosphorylation of Bad and eNOS proteins.

14-3-3 Proteins↗

Does routine serial computed tomography of the head influence management of traumatic brain injury? A prospective evaluation.

BACKGROUND: Computed tomography (CT) of the head is the current standard for diagnosing intracranial pathology following blunt head trauma. It is common practice to repeat the head CT to evaluate any progression of injury. Recent retrospective reviews have challenged the need for serial head CT after traumatic brain injury (TBI). This study intends to prospectively examine the value of routine serial head CT after TBI. METHODS: Consecutive adult blunt trauma patients with an abnormal head CT admitted to an urban, Level I trauma center from January 2003 to September 2003 were prospectively studied. Variables collected included: initial head CT results, indication for repeat head CT (routine versus neurologic change), number and results of repeat head CT scans, and clinical interventions following repeat head CT. RESULTS: Over the 9-month period, there were 128 patients admitted with an abnormal head CT after sustaining blunt trauma. The 16 patients who died within 24 hours and the 12 patients who went directly to craniotomy were excluded. The remaining 100 patients make up the study population. Abnormal head CT findings were subarachnoid hemorrhage (47%), intraparenchymal hemorrhage (37%), subdural hematoma (28%), contusion (14%), epidural hematoma (11%), intraventricular hemorrhage (3%), and diffuse axonal injury (2%). Overall, 32 patients (32%) had only the admission head CT, while 68 patients (68%) underwent 90 repeat CT scans. Of the repeat head CT scans, 81 (90%) were performed on a routine basis without neurologic change. The remaining 9 (10%) were performed for a change in Glasgow Coma Scale (n = 5), change in intracranial pressure (n = 1), change in Glasgow Coma Scale and intracranial pressure (n = 1), change in pupil size (n = 1), or sudden appearance of a headache (n = 1). Three patients had their care altered after repeat head CT: two underwent craniotomy and one was started on barbiturate therapy. All three patients had their repeat head CT after neurologic change (decrease in Glasgow Coma Scale in 2 and increase in intracranial pressure in 1). CONCLUSIONS: Serial head CT is common after TBI. Most repeat head CT scans are performed on a routine basis without neurologic change. Few patients with TBI have their management altered after repeat head CT, and these patients have neurologic deterioration before the repeat head CT. The use of routine serial head CT in patients without neurologic deterioration is not supported by the findings of this study.

Adult↗

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

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.

Animals↗

Rhabdomyolysis after penetrating trauma.

Rhabdomyolysis (RHAB) is a known complication following blunt trauma. RHAB after penetrating trauma has not been studied. The objective of this study was to evaluate the incidence, risk factors, and complications of RHAB following penetrating trauma. Over a 5-year period, penetrating trauma patients admitted to our intensive care unit (ICU) were studied. Significant RHAB was defined as a CK level of 5000 U/L or higher. There were 873 patients (29 +/- 12 years old, 92% male), of whom 767 (88%) had abnormal CK levels (range 520-165,943 U/L), and 111 patients (13%) developed significant RHAB. Victims of penetrating trauma who sustain vascular and severe extremity injury are at a sixfold increased risk to develop significant RHAB. Patients with significant RHAB had a higher rate of renal failure (23% vs 7%, P < 0.0001) and longer ICU stay (15 +/- 26 days vs 8 +/- 12 days, P < 0.0001). CK elevations and significant RHAB are common after penetrating trauma. Patients who sustain vascular and severe extremity injury as a result of their penetrating wounds are at high risk to develop significant RHAB, resulting in renal failure and prolonged ICU stay. Therefore, critically injured penetrating trauma patients should be routinely screened with CK levels.

Adolescent↗

Thromboprophylaxis does not protect severely injured patients against pulmonary embolism.

The existing evidence on the effectiveness of thromboprophylaxis after trauma is conflicting. Although prophylaxis with heparin and/or sequential compression devices is practiced widely, many studies failed to document a clear benefit. A recent meta-analysis suggests that prophylaxis does not reduce posttraumatic deep venous thrombosis rates compared to no prophylaxis. The objective of this prospective study is to examine if the use of thromboprophylaxis prevents posttraumatic pulmonary embolism (PE). Sixty-four critically injured patients with clinical evidence of PE were studied by computed tomographic pulmonary angiography and/or conventional pulmonary angiography. PE was diagnosed in 24 (37.5%) patients. Patients with PE were similar to patients without PE with regard to demographics, injury type and severity, operations, and mortality. Thromboprophylaxis was used with equal frequency between PE and no-PE patients (71% vs 80%, P = 0.4). The type of prophylaxis used was similar between patients with PE (17% heparin, 71% sequential compression devices, 17% combination) and patients without PE (32%, 57%, and 10%, respectively; P = 0.16, 0.28, 0.69, respectively). Current methods of posttraumatic thromboprophylaxis may be inadequate. Practices from nontrauma populations have been erroneously extrapolated to the unique trauma population. To reduce the rate of PE after trauma, new methods of thromboprophylaxis should be considered.

Adult↗

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↗

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↗

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↗

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↗

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↗