Betty J. Tsuei

Arginase I Expression and Activity in Human Mononuclear Cells After Injury

ObjectiveTo determine the effect of trauma on arginase, an arginine-metabolizing enzyme, in cells of the immune system in humans. Summary Background DataArginase, classically considered an enzyme exclusive to the liver, is now known to exist in cells of the immune system. Arginase expression is induced in these cells by cytokines interleukin (IL) 4, IL-10, and transforming growth factor beta, corresponding to a T-helper 2 cytokine profile. In contrast, nitric oxide synthase expression is induced by IL-1, tumor necrosis factor, and gamma interferon, a T-helper 1 cytokine profile. Trauma is associated with a decrease in the production of nitric oxide metabolites and a state of immunosuppression characterized by an increase in the production of IL-4, IL-10, and transforming growth factor beta. This study tests the hypothesis that trauma increases arginase activity and expression in cells of the immune system. MethodsSeventeen severely traumatized patients were prospectively followed up in the intensive care unit for 7 days. Twenty volunteers served as controls. Peripheral mononuclear cells were isolated and assayed for arginase activity and expression, and plasma was collected for evaluation of levels of arginine, citrulline, ornithine, nitrogen oxides, and IL-10. ResultsMarkedly increased mononuclear cell arginase activity was observed early after trauma and persisted throughout the intensive care unit stay. Increased arginase activity corresponded with increased arginase I expression. Increased arginase activity coincided with decreased plasma arginine concentration. Plasma arginine and citrulline levels were decreased throughout the study period. Ornithine levels decreased early after injury but recovered by postinjury day 3. Increased arginase activity correlated with the severity of trauma, early alterations in lactate level, and increased levels of circulating IL-10. Increased arginase activity was associated with an increase in length of stay. Plasma nitric oxide metabolites were decreased during this same period. ConclusionsMarkedly altered arginase expression and activity in cells of the human immune system after trauma have not been reported previously. Increased mononuclear cell arginase may partially explain the benefit of arginine supplementation for trauma patients. Arginase, rather than nitric oxide synthase, appears to be the dominant route for arginine metabolism in immune cells after trauma.

An analgesia-delirium-sedation protocol for critically ill trauma patients reduces ventilator days and hospital length of stay.

BACKGROUND Analgesics and sedatives are required to maintain a calm and comfortable mechanically ventilated injured patient. Continuous sedative infusions have been shown to lengthen mechanical ventilation and hospital length of stay. Daily interruption of sedative infusions may reduce both of these variables. Implementation of an Analgesia-Delirium-Sedation (ADS) Protocol using objective assessments with a goal of maintaining an awake and comfortable patient may obviate the need for daily interruption of infusions in critically ill trauma patients. We examined the effects of such a protocol on ventilator duration, intensive care unit (ICU) length of stay, hospital slength of stay, and medication requirements. METHODS A multidisciplinary team designed the protocol. Objective measures of pain (visual/objective pain assessment scale-VAS/OPAS), agitation (Richmond Agitation-Sedation Scale-RASS), and delirium [Confusion Assessment Method {CAM-ICU}] were used. Medications were titrated to a RASS of -1 to +1 and VAS/OPAS <4. Haloperidol was used to treat delirium in CAM-ICU positive patients. Retrospective review of the local Project IMPACT database for a 6-month period in 2004 was compared with the same seasonal period in 2006 in which the ADS protocol was used. All mechanically ventilated trauma patients receiving infusions of narcotic, propofol, or benzodiazepine were included. Age, APACHE II score, Injury Severity Score, ventilator days, ventilator-free days at day 28, ICU length of stay, and hospital length of stay are reported as median values (interquartile range). Medication usage is reported as mean values (+/-SD). Differences in data were analyzed using Wilcoxons rank-sum test or t test, as appropriate. Gender, mortality, and mechanism of injury were analyzed using chi analysis. RESULTS A total of 143 patients were included. Patients who died during their hospitalization were excluded except in the analysis of ventilator-free days at day 28. After exclusions, 61 patients were in the control group and 58 in the protocol group. The median duration of mechanical ventilation in the protocol group was 1.2 days (0.5-3.0) which was significantly reduced compared with 3.2 days (1.0-12.9) in the control group (p = 0.027). Analysis of ventilator-free days at day 28 found that the protocol group had 26.4 ventilator-free days (13.9-27.4) compared with 22.8 days (10.5-26.9) in the control group (p = 0.007). The median ICU length of stay was 5.9 days (2.3-18.2) in the control group and 4.1 days (2.5-8.3) in the protocol group (p = 0.21). Hospital length of stay was 12 days (7-17) in the protocol group in contrast to 18 days (10-27) in the control group (p = 0.036). Opiate equivalents and propofol use per patient was significantly reduced in the protocol group from 2,465 mg (+/-1,242 mg) to 1,641 mg (+/-1,250 mg) and 19,232 mg (+/-22,477 mg) to 10,057 (+/-14,616 mg), respectively (p < 0.001, p = 0.01). CONCLUSION An objective assessment- based ADS protocol without daily interruption of medication infusion decreases ventilator days and hospital length of stay in critically ill trauma patients.

The routine use of sonography in penetrating torso injury is beneficial.

BACKGROUND Torso sonography (focused assessment with sonography for trauma [FAST]) has been added to our protocols for the evaluation of penetrating torso injury. The purpose of this study was to evaluate our recent experience and determine whether the use of FAST is beneficial. METHODS From January 1999 to January 2000, patients with penetrating torso injury and no clinical indication for surgery were evaluated by sonography with a selective use of other investigations. FAST consisted of sonographic views of the peritoneum and/or pericardium to determine the presence or absence of fluid. RESULTS During the study period, there were 238 victims of penetrating injury assessed by our trauma service, and sonography was performed in 72 (30%) patients as per our protocols. There were 31 stab, 37 gunshot/shotgun and, and 4 puncture wounds. Thirty-eight patients had peritoneal views, 6 patients had pericardial views, and 28 patients had both pericardial and peritoneal views obtained. Thirteen of 66 patients had free fluid in the peritoneal cavity and 12 of the 13 patients had a therapeutic laparotomy. No peritoneal fluid was seen in 53 of 66 patients, of whom 6 had abdominal injuries, 5 requiring surgery for diaphragm or bowel injuries. The sensitivity of FAST alone for abdominal injury was 67%, specificity was 98%, positive predictive value was 92%, and negative predictive value was 89%. Pericardial fluid was seen in 3 of 34 patients; one had a heart wound and two had negative pericardial windows. All 31 patients without pericardial fluid recovered without surgery. CONCLUSION The routine use of sonography in penetrating torso injury is beneficial. The detection of pericardial or peritoneal fluid is clinically useful. However, a negative FAST examination does not exclude abdominal injury, such as a diaphragm or hollow viscus wound, and further investigation or close follow-up is required.

Alterations in arginine metabolic enzymes in trauma

Arginine is the sole substrate for nitric oxide (NO) synthesis by NO synthases (NOS) and promotes the proliferation and maturation of human T-cells. Arginine is also metabolized by the enzyme arginase, producing urea and ornithine, the precursor for polyamine production. We sought to determine the molecular mechanisms regulating arginase and NOS in splenic immune cells after trauma. C3H/HeN mice underwent laparotomy as simulated moderate trauma or anesthesia alone (n = 24 per group). Six, 12, 24, or 48 h later, 6 animals from each group were sacrificed, and splenectomy was performed and plasma collected. Six separate animals had neither surgery nor anesthesia and were sacrificed to provide resting values (t = 0 h). Spleen arginase I and II and iNOS mRNA abundance, arginase I protein expression, and arginase activity were determined. Plasma NO metabolites (nitrite + nitrate) were also measured. Trauma increased spleen arginase I protein expression and activity (P = 0.01) within 12 and for at least 48 h after injury and coincided with up-regulated arginase I mRNA abundance at 24 h. Neither arginase II nor iNOS mRNA abundance in the spleen was significantly increased by trauma at 24 h. Plasma nitrite + nitrate was decreased in animals 48 h post-injury compared to anesthesia controls (P < 0.05). Trauma induces up-regulation of arginase I gene expression in splenic immune cells within 24 h of injury. Arginase II is not significantly up-regulated at that time point. Arginase I, rather than iNOS appears to be the dominant route for arginine metabolism in splenic immune cells 24 h after trauma.

Surgery induces human mononuclear cell arginase I expression

BACKGROUND Arginase is a metabolic enzyme for the amino acid arginine that participates in the immune response to trauma. We hypothesize that surgical trauma induces arginase expression and activity in the human immune system. METHODS Peripheral mononuclear cell (MNC) arginase activity and expression and plasma nitric oxide metabolites and interleukin (IL)-10 were measured in patients undergoing elective general surgery. Twenty-two healthy volunteers served as a comparison population. RESULTS MNC arginase activity increased within 6 hours of surgery (p < 0.05) and coincided with increased arginase I protein expression. Plasma nitric oxide metabolites decreased significantly postoperatively (p < 0.05). Patients lacking an elevation in IL-10 failed to demonstrate increased MNC arginase activity. CONCLUSION Increased MNC arginase expression may contribute to postsurgical immune dysfunction by affecting arginine use and availability and nitric oxide metabolism in the immune system. Plasma IL-10 may play a role in regulating MNC arginase activity.

Telemedicine: a solution to the followup of rural trauma patients?

BACKGROUND Outpatient followup of rural trauma patients is problematic for physicians and patients. Our hypothesis was that telemedicine-based followup of trauma patients discharged to remote areas is feasible and is associated with high patient and physician satisfaction. STUDY DESIGN We chose 11 counties in Kentucky surrounding a remote telemedicine site as our region of interest. Any adult trauma patient who was discharged from our Level I trauma center to this geographic region was eligible to have routine followup appointment(s) at the TeleTrauma Clinic. Patients were examined and interviewed with the assistance of a nurse, an electronic stethoscope, and a close-up imaging instrument. Radiographs performed at the telemedicine site were viewed. Patients and physicians completed a survey after the appointment. RESULTS To date, we have conducted 22 telemedicine-based followup assessments of trauma patients. The average age and Injury Severity Score were 42 years and 18, respectively. Plain radiographs were reviewed in 13 cases. Our patient surveys indicated a high degree of satisfaction with the teleappointment. In 15 of 22 patients, no further clinical followup was arranged. The differences in travel distances and times for an appointment at the TeleTrauma Clinic versus an appointment at our Level I trauma center were significant. The average and median duration of the appointments was 14 minutes. All telemedicine encounters were done by two physicians, who recorded a high level of satisfaction. CONCLUSIONS Our early experience with the outpatient followup of remote trauma victims by telemedicine is encouraging. Patient surveys indicate a high degree of satisfaction. As a result of our favorable experience, telemedicine-based followup may be expanded to other regions of Kentucky.

Enteral Nutrition in Patients With an Open Peritoneal Cavity

Recent surgical advances have led to the increased survival of critically ill patients requiring postoperative nutritional supplementation. One technique, which has been increasingly used, is that of the open peritoneal cavity. In these cases, the peritoneum is left open, and the viscera are protected with a temporary dressing until the abdomen can be closed. The aim of this study was to evaluate the efficacy and tolerance of enteral nutrition in patients who need open peritoneal cavity management techniques. Patients at a tertiary referral center requiring the use of open peritoneal cavity management who received at least 4 days of enteral nutrition were included in the study. Retrospective data were collected on patients admitted between January 1999 and December 2000, and prospective data were collected on patients between January and May 2001. Energy expenditure and actual caloric and protein intake were determined in all patients. Prealbumin levels and nitrogen balance studies were analyzed when available. Intolerance, defined as diarrhea or gastric reflux, was also evaluated. Average daily total caloric intake was 77 +/- 27%, and average daily protein intake was 68 +/- 24% of estimated needs. Initial serum prealbumin levels were low and remained below normal but increased in some patients during the study. Average nitrogen balance studies from 3 patients was -15 +/- 9.7 g/d. Diarrhea and gastric reflux occurred in 42% and 36% of patients, respectively, and were easily treated. Enteral nutrition can be effectively used in patients requiring open peritoneal cavity management after laparotomy. Overall, enteral nutrition is relatively well tolerated in this patient population.

Emergency airway placement by EMS providers: comparison between the King LT supralaryngeal airway and endotracheal intubation.

INTRODUCTION The ever-present risk of mass casualties and disaster situations may result in airway management situations that overwhelm local emergency medical services (EMS) resources. Endotracheal intubation requires significant user education/training and carries the risk of malposition. Furthermore, personal protective equipment (PPE) required in hazardous environments may decrease dexterity and hinder timely airway placement. Alternative airway devices may be beneficial in these situations. OBJECTIVE The objective of this study was to evaluate the time needed to place the King LT Supralaryngeal Airway compared to endotracheal intubation when performed by community EMS personnel with and without PPE. METHODS Following training, 47 EMS personnel were timed placing both endotracheal tubes and the King LT supralaryngeal airway in a simulator mannikin. The study participants then repeated this exercise wearing PPE. RESULTS The EMS personnel wearing PPE took significantly longer to place an endotracheal tube than they did without protective equipment (53.4 seconds and 39.5 seconds, p <0.002). The time to place the King LT was significantly faster than the placement of the endotracheal tube without protective equipment (18.4 seconds and 39.5 seconds, respectively, p <0.00003). There also were statistically significant differences between the time required to place the King LT and endotracheal tube in EMS personnel wearing protective equipment (19.7 seconds and 53.4 seconds, p <0.000007). CONCLUSIONS The King LT Supralaryngeal Airway device may be advantageous in prehospital airway management situations involving multiple patients or hazardous environments. In this study, its insertion was faster than endotracheal intubation when performed by community EMS providers.

Early treatment of blunt cerebrovascular injury with concomitant hemorrhagic neurologic injury is safe and effective.

Background: Early pharmacologic treatment for blunt cerebrovascular injury (BCVI) is often withheld when concomitant traumatic brain injury or cervical spinal cord injury occurs. This study examines the safety and efficacy of early treatment for patients with both BCVI and traumatic neurologic injury (TNI). Methods: Ten-year retrospective review of patients with BCVI and a TNI was performed. Stroke outcomes for those treated with pharmacologic therapy for their BCVI were compared with those not treated. In addition, the likelihood of worsening of TNI was determined for those exposed to pharmacologic therapy compared with those not exposed. Multivariate logistic regression techniques were used to analyze adjusted odds ratio for stroke risk. Results: Seventy-seven patients were identified with BCVI + TNI. Strokes occurred in 27% patients with 3 of 21 (14%) strokes present at arrival. There were no differences in baseline characteristics between groups. Stroke rate was higher in the untreated group compared with treated (57% vs. 4%, p < 0.0001). On multivariate regression, treatment status was the most significant stroke predictor (adjusted odds ratio 4.4, 3.0–6.5, p < 0.0001, c-stat 0.93). There was no difference in risk of hemorrhagic deterioration of traumatic brain injury based on pharmacologic exposure versus no exposure (5% vs. 6%, p = 0.6). Likewise, no patient with spinal cord injury worsened as a result of pharmacologic exposure. Of the potentially preventable strokes, 24% (4 of 17) resulted in a stroke-related death and all four deaths occurred in the untreated group. Conclusion: The benefit of early treatment for BCVI markedly outweighs the risk of treatment for patients suffering concomitant BCVI and hemorrhagic neurologic injury. Level of Evidence: III.

Risk factors for relapse of ventilator-associated pneumonia in trauma patients.

BACKGROUND Our goal was to define risk factors for ventilator-associated pneumonia (VAP) relapse and examine the implications, if any, for initial therapy in trauma patients. METHODS Trauma patients cared for in the surgical intensive care unit during a 48-month period with confirmed VAP recurrence were evaluated. Recurrent VAP was defined as a positive quantitative culture (> or = 10(4) colony-forming units/mL in a bronchoalveolar lavage or protected catheter lavage specimen) > or = 4 days after initiation of antibiotics for the primary episode. Recurrence with at least one of the initial causative pathogens was defined as a relapse. Initial causal pathogen, Acute Physiology and Chronic Health Evaluation II score, injury severity score, Glasgow Coma Score (GCS), age, white blood cell count (WBC), and duration of hospital stay before diagnosis were analyzed in univariate and multivariate regression models. RESULTS A total of 55 patients met the criteria of recurrent VAP. Of these 55 recurrences, 19 (35%) were relapses. Acute Physiology and Chronic Health Evaluation II score, injury severity score, and GCS were not associated with VAP relapse by univariate analyses. Patients who relapsed had primary VAP involving nonfermenting gram-negative bacilli (NFGNB) (Acinetobacter, Pseudomonas, and Stenotrophomonas species) more frequently than other organisms (68% vs. 32%, p = 0.001). Primary VAP with NFGNB was found to be a significant predictor of VAP relapse by univariate and multivariate logistic regression analysis (OR = 5.1, p = 0.003; OR = 4.63, p = 0.005, respectively). CONCLUSIONS There is a high rate of VAP relapse associated with primary infection by NFGNB, suggesting initial treatment failure. Trauma patients with primary VAP involving these organisms may benefit from increased surveillance for relapse.