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Biomedical subjects

Rosemary A Kozar

Publications and source records attributed to Rosemary A Kozar.

At least 19 recordsLinked to original sources
PubMed2007

Fresh frozen plasma should be given earlier to patients requiring massive transfusion.

BACKGROUND: Acidosis, hypothermia, and coagulopathy were identified more than 20 years ago as a deadly triad for patients presenting with exsanguinating hemorrhage. This led to fundamental changes in initial management of severely injured patients. Despite major advances, hemorrhage remains a leading cause of early death in trauma patients. Recent studies report most severely injured patients to be coagulopathic at admission, before resuscitation interventions, and that traditional massive transfusion practice grossly underestimates needs. The hypothesis for this study is that our pre-intensive care unit (ICU) massive transfusion (MT) protocol does not adequately correct coagulopathy, and that early uncorrected coagulopathy is predictive of mortality. METHODS: Data maintained in our Trauma Research Database were reviewed. Univariate logistic regression analysis was used to analyze the association of early ICU international normalized ratio (INR) and outcomes, including survival. RESULTS: Ninety-seven of 200 patients admitted during 51 months (ending January 2003) and resuscitated using our standardized ICU shock resuscitation protocol received MT (> or =10 units packed red blood cells [PRBC]) during hospital day 1 (age, 39 +/- 2; ISS, 29 +/- 1; survival, 70%.) All patients required emergency operating room and/or interventional radiology procedures and arrived in the ICU 6.8 +/- 0.3 hours after admission. Coagulopathy, present at hospital admission (pre-ICU INR, 1.8 +/- 0.2), persisted at ICU admission (initial ICU INR, 1.6 +/- 0.1). Pre-ICU resuscitation, 9 +/- 1 L crystalloid fluid, 12 +/- 1 units PRBC, 5 +/- 0.4 units fresh frozen plasma (FFP), was consistent with our MT protocol by which FFP was not given until after 6 units PRBC. ICU resuscitation involved 11 +/- 1 L lactated Ringer's solution (LR) and 10 +/- 1 units PRBC. Mean pH was normal within 8 hours. Mean temperature increased from approximately 35 degrees C to >37 degrees C within 4 hours. In the ICU during resuscitation, patients received 10 +/- 1 units FFP for coagulopathy; the ratio of FFP:PRBC was 1:1. Mean INR decreased to 1.4 +/- 0.03 within 8 hours and remained nearly constant for the remaining 16 hours of ICU resuscitation, indicating moderate coagulopathy. Statistical analysis found severity of coagulopathy (INR) at ICU admission associated with survival outcome (p = 0.02; area under receiver operator curve [ROC] = 0.71.) CONCLUSION: These data indicate acidosis and hypothermia to be well managed. Coagulopathy was not corrected in the ICU despite adherence to pre-ICU MT and ICU protocols, likely because of inadequate pre-ICU intervention. More aggressive pre-ICU intervention to correct coagulopathy may be effective in decreasing PRBC requirement during ICU resuscitation, and, because of the association with increased mortality, could improve outcome. We have revised our pre-ICU MT protocol to emphasize early FFP in a FFP:PRBC ratio of 1:1. We think that treatment of coagulopathy can be improved with the development of standardized protocols, both empiric and data driven.

Adult↗
PubMed2006

Risk factors for hepatic morbidity following nonoperative management: multicenter study.

HYPOTHESIS: Early risk factors for hepatic-related morbidity in patients undergoing initial nonoperative management of complex blunt hepatic injuries can be accurately identified. DESIGN: Multicenter historical cohort. SETTING: Seven urban level I trauma centers. PATIENTS: Patients from January 2000 through May 2003 with complex (grades 3-5) blunt hepatic injuries not requiring laparotomy in the first 24 hours. INTERVENTION: Nonoperative treatment of complex blunt hepatic injuries. MAIN OUTCOME MEASURES: Complications and treatment strategies. RESULTS: Of 699 patients with complex blunt hepatic injuries, 453 (65%) were treated nonoperatively. Overall, 61 patients (13%) developed 87 hepatic complications including bleeding (38), biliary (bile peritonitis, 7; bile leak, 9; biloma, 11; biliary-venous fistula, 1; and bile duct injury, 1), abdominal compartment syndrome (5), and infections (abscess, 7; necrosis, 2; and suspected abdominal sepsis, 6), which required 86 multimodality treatments (angioembolization, 32; endoscopic retrograde cholangiopancreatography and stenting, 9; interventional radiology drainage, 16; paracentesis, 1; laparotomy, 24; and laparoscopy, 4). Hepatic complications developed in 5% (13 of 264) of patients with grade 3 injuries, 22% (36 of 166) of patients with grade 4 injuries, and 52% (12 of 23) of patients with grade 5 injuries. Univariate analysis revealed 24-hour crystalloid, total and first 24-hour packed red blood cells, fresh frozen plasma, platelet, and cryoprecipitate requirements and liver injury grade to be significant but only liver injury grade (grade 4 odds ratio, 4.439; grade 5 odds ratio, 12.001) and 24-hour transfusion requirement (odds ratio, 6.446) predicted complications by multivariable analysis. CONCLUSIONS: Nonoperative management of high-grade liver injuries is associated with significant morbidity and correlates with grade of liver injury. Screening patients with transfusion requirements and high-grade injuries may result in earlier diagnosis and treatment of hepatic-related complications.

Abdominal Injuries↗
PubMed2006

A multidisciplinary clinical pathway decreases rib fracture-associated infectious morbidity and mortality in high-risk trauma patients.

BACKGROUND: We initiated a multidisciplinary clinical pathway targeting patients greater than 45 years of age with more than 4 rib fractures. The purpose of the current study was to evaluate the effect of this pathway on infectious morbidity and mortality. METHODS: This was a prospective cohort study. Data evaluated included patient demographics, injury characteristics, pain management details, lengths of stay, morbidity, and mortality. Univariate and multivariate analyses were performed using a significance level of P < .05. RESULTS: When adjusting for age, injury severity score, and number of rib fractures, the clinical pathway was associated with decreased intensive care unit length of stay by 2.4 days (95% confidence interval [CI] -4.3, -0.52 days, P = .01) hospital length of stay by 3.7 days (95% CI -7.1, -0.42 days, P = .02), pneumonias (odds ratio [OR] 0.12, 95% CI 0.04 to 0.34, P < .001), and mortality (OR 0.37, 95% CI 0.13 to 1.03, P = .06). CONCLUSIONS: Implementation of a rib fracture multidisciplinary clinical pathway decreased mechanical ventilator-dependent days, lengths of stay, infectious morbidity, and mortality.

Aged↗
PubMed2006

Conventional dose hypertonic saline provides optimal gut protection and limits remote organ injury after gut ischemia reperfusion.

BACKGROUND: Hypertonic saline (HS) resuscitation prevents neutrophil mediated injury after shock. The optimal dose is not known, but appears as a result of osmotic stress. We hypothesized that a dose dependent effect exists related to increasing tonicity and that the optimal gut protective dose would provide better protection against remote organ injury than large volume isotonic crystalloids. METHODS: In experiment 1, rats were assigned to controls (sham/no resuscitation, sham/4 mL/kg 7.5% HS, superior mesenteric artery occlusion [SMAO]/no resuscitation), SMAO/equal volume (4 mL/kg 0.9% NS, 4 mL/kg 2.5% HS, 4 mL/kg 5% HS, 4 mL/kg 7.5% HS and 4 mL/kg 10% HS) or SMAO/equal sodium (33 mL/kg 0.9% NS, 12 mL/kg 2.5% HS, 6 mL/kg 5% HS, 4 mL/kg 7.5% HS, and 3 mL/kg 10% HS). In experiment 2, rats were assigned to the same control groups, and to either SMAO/NS (33 mL/kg 0.9% NS, equal salt load) or SMAO/HS (4 mL/kg 7.5% HS). The SMAO was clamped for 60 minutes and boluses given 5 minutes before clamp removal. After 6 hours of reperfusion, ileum and lungs were harvested for analysis of histologic injury, myeloperoxidase (MPO) as an index of neutrophil mediated injury, and serum ALT and AST drawn as markers of liver injury. RESULTS: In experiment 1, equal volume and equal sodium decreased injury and inflammation with increasing tonicity in a dose dependent fashion, with the optimal effect seen at 7.5%. In experiment 2, NS resuscitation resulted in minimal improvement of SMAO-induced lung injury and inflammation or increases in serum ALT and AST whereas HS resuscitation significantly decreased these parameters. CONCLUSION: The protective effect of HS is related to increased tonicity. While NS had little effect on SMAO-induced remote organ injury, optimal dose HS resuscitation was quite protective. This supports the growing evidence that HS protection may be because of its gut protective effects.

Analysis of Variance↗
PubMed2006

Nutrition support in adult trauma patients.

Nutrition supplementation is paramount to the care of severely injured patients. Despite its widespread use in trauma patients, many areas of clinical practice remain controversial. The purpose of this paper is to critically review the literature studying the use of enteral vs parenteral nutrition (PN) and to provide the rationale for early enteral nutrition. Additional controversies confronting clinicians are reviewed, including the use of immune-enhancing agents and the optimal site for enteral nutrition delivery (gastric vs small intestinal). Evidence-based recommendations for clinical practice are presented when available.

Critical Illness↗
PubMed2005

Potential targets to encourage a surgical career.

BACKGROUND: Our goal was to identify factors that can be targeted during medical education to encourage a career in surgery. STUDY DESIGN: We conducted a cross-sectional survey of first and fourth year classes in a Liaison Committee on Medical Education-accredited medical school. Students scored 19 items about perceptions of surgery using a Likert-type scale. Students also indicated their gender and ranked their top three career choices. RESULTS: There were 121 of 210 (58%) first year and 110 of 212 (52%) fourth year students who completed the survey. First year students expressed a positive correlation between surgery and career opportunities, intellectual challenge, performing technical procedures, and obtaining a residency position, although length of training, work hours, and lifestyle during and after training were negatively correlated with choosing surgery. Fourth year student responses correlated positively with career and academic opportunities, intellectual challenge, technical skills, role models, prestige, and financial rewards. Factors that correlated negatively were length of training, residency lifestyle, hours, call schedule, and female gender of the student respondent. Forty-four percent of first year male students expressed an interest in surgery versus 27% of fourth year male students (p < 0.04). Eighteen percent of first year female students expressed an interest in surgery versus 5% of fourth year female students (p < 0.006). CONCLUSIONS: Lifestyle issues remain at the forefront of student concerns. Intellectual challenge, career opportunities, and technical skills are consistently recognized as strengths of surgery. Additionally, fourth year students identify role models, prestige, and financial rewards as positive attributes. Emphasizing positive aspects may facilitate attracting quality students to future careers in surgery.

Algorithms↗
PubMed2005

Peroxisome proliferator-activated receptor gamma mediates protection against cyclooxygenase-2-induced gut dysfunction in a rodent model of mesenteric ischemia/reperfusion.

Cyclooxygenase (COX)-2 has been identified as an important mediator elaborated during ischemia/reperfusion, with pro- and anti-inflammatory properties having been reported. As the role of COX-2 in the small intestine remains unclear, we hypothesized that COX-2 expression would mediate mesenteric ischemia/reperfusion-induced gut injury, inflammation, and impaired transit and that these deleterious effects could be reversed by the selective COX-2 inhibitor, N-[2-(cyclohexyloxy)-4-nitrophenyl] methanesulphanamide (NS-398). Additionally, we sought to determine the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in mediating protection by NS-398 in this model. Rats underwent sham surgery or were pretreated with NS-398 (3, 10, or 30 mg/kg) intraperitoneally 1 h before 60 min of superior mesenteric artery occlusion and 30 min to 6 h of reperfusion. In some experiments, NS-398 (30 mg/kg) was administered postischemia. Ileum was harvested for COX-2 mRNA and protein, PGE2, myeloperoxidase (inflammation), histology (injury), intestinal transit and PPARgamma protein expression, and DNA-binding activity. COX-2 expression and PGE2 production increased after mesenteric ischemia/reperfusion and were associated with gut inflammation, injury, and impaired transit. Inhibition of COX-2 by NS-398 (30 mg/kg, but not 3 or 10 mg/kg) not only reversed the deleterious effects of COX-2, but additionally induced expression and nuclear translocation of PPARgamma. NS-398 given postischemia was equally protective. In conclusion, COX-2 may function as a proinflammatory mediator in a rodent model of mesenteric ischemia/reperfusion. Reversal of gut inflammation, injury, and impaired transit by high-dose NS-398 is associated with PPAR activation, suggesting a potential role for PPAR-gamma in shock-induced gut protection.

Active Transport, Cell Nucleus↗
PubMed2005

Immune-enhancing enteral nutrients differentially modulate the early proinflammatory transcription factors mediating gut ischemia/reperfusion.

BACKGROUND: Recent reports suggest that enteral diets enriched with arginine may be harmful by enhancing inflammation. This is consistent with our gut ischemia/reperfusion (I/R) model in which arginine induced the proinflammatory mediator inducible nitric oxide synthase and resulted in injury and inflammation whereas glutamine was protective. We now hypothesize that arginine and glutamine differentially modulate the early proinflammatory transcription factors activated by gut I/R. METHODS: At laparotomy, jejunal sacs were filled with either 60 mmol/L glutamine, arginine, or an iso-osmotic control followed by 60 minutes of superior mesenteric artery occlusion and 6 hours of reperfusion and compared with shams. Jejunum was harvested for nuclear factor (NF)-kappaB and activator protein-1 (AP-1) measured by electrophoretic mobility shift assay and c-jun and c-fos (AP-1 family) by supershift. RESULTS: Both NF-kappaB and AP-1 were activated by gut I/R. Arginine and glutamine had no differential effect on NF-kappaB, whereas AP-1 expression (c-jun but not c-fos) was markedly enhanced by arginine and significantly lessened by glutamine. CONCLUSION: Arginine enhanced expression of the early proinflammatory transcription factor AP-1 but not NF-kappaB. This represents a novel mechanism by which arginine may be harmful when administered to critically ill patients.

Analysis of Variance↗
PubMed2005

Hypertonic saline resuscitation after mesenteric ischemia/reperfusion induces ileal apoptosis.

BACKGROUND: We have previously demonstrated that hypertonic saline (HS) resuscitation decreased inflammation and mucosal injury after mesenteric ischemia/reperfusion (I/R). In contrast to I/R cell necrosis, apoptosis provides controlled cell death that minimizes inflammation. We therefore hypothesized that HS resuscitation after mesenteric I/R would induce apoptosis and decrease mucosal injury. METHODS: Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then received no resuscitation or resuscitation with 4 mL/kg of HS, 4 mL/kg of lactated Ringer's (LR) solution (equal volume), or 32 mL/kg of LR solution (equal salt load). Rats were killed at 6 hours of reperfusion, and ileum was harvested for analysis. DNA fragmentation (apoptosis) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and mucosal injury by histology (Chiu score 0-5). Caspase-3 (proapoptotic mediator) and Bcl-xL (antiapoptotic mediator) protein expression were analyzed by Western immunoblot. RESULTS: SMAO with no resuscitation, SMAO with 4 mL/kg of LR, and SMAO with 32 mL/kg of LR increased apoptosis (quantitated by TUNEL) and I/R-induced mucosal injury (quantitated by Chiu score). This was associated with an increase to similar levels in both proapoptotic caspase-3 and antiapoptotic Bcl-xL protein expression. Moreover, SMAO with 4 mL/kg of HS further increased apoptosis but decreased mucosal injury. This was associated with a differential expression of proapoptotic caspase-3 over antiapoptotic Bcl-xL. CONCLUSION: HS resuscitation after mesenteric I/R significantly increased ileal mucosal apoptosis while decreasing mucosal injury and may represent a novel mechanism by which HS resuscitation after mesenteric I/R reduces inflammation and imparts protection to the gut.

Animals↗
PubMed2005

Complications of nonoperative management of high-grade blunt hepatic injuries.

BACKGROUND: Nonoperative management of blunt hepatic injuries is highly successful. Complications associated with high-grade injuries, however, have not been well characterized. The purpose of the present study was therefore to define hepatic-related complications and associated treatment modalities in patients undergoing nonoperative management of high-grade blunt hepatic injuries. METHODS: Three hundred thirty-seven patients from two regional Level I trauma centers with grade 3 to 5 blunt hepatic injuries during a 40-month period were reviewed. Complications and treatment of hepatic-related complications in patients not requiring laparotomy in the first 24 hours were identified. RESULTS: Of 337 patients with a grade 3 to 5 injury, 230 (68%) were managed nonoperatively. There were 37 hepatic-related complications in 25 patients (11%); 63% (5 of 8) of patients with grade 5 injuries developed complications, 21% (19 of 92) of patients with grade 4 injuries, but only 1% (1 of 130) of patients with grade 3 injuries. Complications included bleeding in 13 patients managed by angioembolization (n = 12) and laparotomy (n = 1), liver abscesses in 2 patients managed with computed tomography-guided drainage (n = 2) and subsequent laparotomy (n = 1). In one patient with bleeding, hepatic necrosis followed surgical ligation of the right hepatic artery and required delayed hepatic lobectomy. Sixteen biliary complications were managed with endoscopic retrograde cholangiopancreatography and stenting (n = 7), drainage (n = 5), and laparoscopy (n = 4). Three patients had suspected abdominal sepsis and underwent a negative laparotomy, whereas an additional three patients underwent laparotomy for abdominal compartment syndrome. CONCLUSION: Nonoperative management of high-grade liver injuries can be safely accomplished. Mortality is low; however, complications in grade 4 and 5 injuries should be anticipated and may require a combination of operative and nonoperative management strategies.

Adult↗
PubMed2005

Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury.

Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min) followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham 24-h group, a sham late IPC + IR group (sham IPC followed by additional reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h, and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h, transit was determined and expressed as the mean geometric center. Ileum was harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1; mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4) and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4 +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1). Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.

Animals↗
PubMed2005

The association between Chance fractures and intra-abdominal injuries revisited: a multicenter review.

The association between Chance fractures and intra-abdominal injuries is reported to be as high as 89 per cent. Because prior studies were small series or case reports, we conducted a multicenter review to learn the true association between Chance fractures and intra-abdominal injuries as well as diagnostic trends. Trauma registry data, medical records, and radiology reports from 7 trauma centers were used to characterize 79 trauma patients with Chance fractures. Initial methods of abdominal assessment were computed tomography (CT) scan (79%), clinical examination (16%), and diagnostic peritoneal lavage (DPL) (5%). Twenty-six (33%) patients had intraabdominal injuries of which hollow viscus injuries predominated (22%). Twenty patients (25%) underwent laparotomy. The presence of an abdominal wall contusion and automobile restraint use were highly predictive of intra-abdominal injury and the need for laparotomy. The association between a Chance fracture and intra-abdominal injury is not as high as previously reported. CT scan has become the primary modality to assess the abdominal cavity of patients with Chance fractures, whereas the role of DPL has diminished.

Abdominal Injuries↗
PubMed2004

Preclinical students: who are surgeons?

BACKGROUND: The purpose of the present study was to determine how preclinical medical students formulate their career choice and to determine the origin of negative perceptions regarding surgery as a career. MATERIALS AND METHODS: A qualitative study was performed with second-year medical students voluntarily participating in focus group study. Students with and without an interest in surgery attended. Topics discussed included factors influencing career choice, priorities, perceptions, exposure, and interactions with surgeons. Three investigators conducted independent content analysis. RESULTS: Career choices for students interested in surgery originated primarily from premedical school experiences/interactions with surgeons. In contrast, students not interested in surgery made career choices during medical school and choices were shaped primarily by second-year preceptors. The main priority for students interested in surgery was personal happiness that was perceived as being significantly dependent upon career satisfaction. Students not interested in surgery tended to separate happiness derived from career versus family. Negative perceptions toward surgery were developed and reinforced by media, preceptors, and classmates. All students had minimal exposure to surgeons during preclinical years and generally agreed that increased involvement with surgeons would be beneficial, particularly through preclinical preceptorships. CONCLUSIONS: Career choices of preclinical students interested in surgery were made prior to entering medical school, suggesting that outreach programs to high schools and colleges may beneficial. Negative perceptions about surgery develop through a variety of sources, including fellow classmates, preceptors, and the media. Surgeons need to take responsibility for these perceptions.

Career Choice↗
PubMed2004

Superior mesenteric artery occlusion models shock-induced gut ischemia-reperfusion.

INTRODUCTION: Superior mesenteric artery occlusion (SMAO) is a simple and reproducible model of shock-induced gut ischemia/reperfusion, but some argue that it is not clinically relevant. The purpose of the current study was to compare SMAO to a standard model of controlled hemorrhage (CH) and uncontrolled hemorrhage (UH). METHODS: Rats had femoral lines and a jejunal mucosal laser Doppler placed followed by SMAO (60 min of ischemia, no resuscitation), controlled hemorrhage (40 mm Hg for 60 min, 2:1 resuscitation shed blood and lactated Ringers), or uncontrolled hemorrhage (liver injury, 3:1 resuscitation with lactated Ringers). Base deficit, lactate, and jejunal mucosal flow (as a percentage of baseline) were recorded during ischemia and for 120 min after reperfusion. Jejunal tissue was harvested for morphological evaluation. Comparison among groups was by analysis of variance (ANOVA), and significance was set at P < 0.05. RESULTS: Mucosal blood flow was similar among groups at the onset of reperfusion (CH, 16.9 +/- 5.0% versus UH, 10.9 +/- 3.1% versus SMAO, 13.9 +/- 6.2%) and during the initial period of reperfusion. By 120 min, however, flow in CH (75.4 +/- 2.5%) was significantly higher that in either UH (36.4 +/- 13.1%) or SMAO (31.7 +/- 8.4%). Histological injury was less with CH, while base deficit was significantly higher in CH at the onset of reperfusion (-24 +/- 2 versus UH, -10 +/- 3 and SMAO, -6 +/- 3 mM/L) but comparable by the end (CH, -17 +/- 4 versus UH, -16 +/- 3 and SMAO, -17 +/- 2 mM/L). CONCLUSIONS: SMAO is a clinically relevant model of shock-induced gut ischemia/reperfusion.

Animals↗
PubMed2004

Preload optimization using "starling curve" generation during shock resuscitation: can it be done?

Preload-directed resuscitation is the standard of care in U.S. trauma centers. As part of our standardized protocol for traumatic shock resuscitation, patients who do not respond to initial interventions of hemoglobin replacement and fluid volume loading have optimal preload determined using a standardized algorithm to generate a "Starling curve." We retrospectively analyzed data from 147 consecutive resuscitation protocol patients during the 24 months ending August 2002. Fifty (34%) of these patients required preload optimization, of which the optimization algorithm was completed in 36 (72%). The average age of those who required preload optimization was 44 +/- 3 years vs. 34 +/- 1 years for patients who did not. Execution of the algorithm caused PCWP to increase from 18 +/- 1 mmHg to a maximum of 25 +/- 2 mmHg and CI to increase from 3.2 +/- 0.1 L/min m(-2) to 4.5 +/- 0.4 L/min m(-2). Algorithm logic determined PCWP = 24 +/- 2 to be optimal preload at the maximum CI = 4.8 +/- 0.4, and as the volume loading threshold for the remaining time of the resuscitation process. Starling curve preload optimization was begun 6.5 +/- 0.8 h after start of the resuscitation protocol and required 36 +/- 5 min and 4 +/- 0.4 fluid boluses (1.6 +/- 0.2 L). Comparison of early response of those patients who required preload optimization and those who did not indicated hemodynamic compromise apparent in the 1st 4 h of standardized resuscitation. We conclude that preload optimization using sequential fluid bolus and PCWP-CI measurement to generate a Starling curve is feasible during ICU shock resuscitation, but that there is the disadvantage that increasing and maintaining high PCWP may contribute to problematic tissue edema.

Abdominal Injuries↗
PubMed2004

Enteral glutamine but not alanine maintains small bowel barrier function after ischemia/reperfusion injury in rats.

We previously demonstrated that glucose and glutamine, solutes metabolized by the gut, replenish ATP and enhance gut function compared with alanine, a solute not metabolized by the gut, following mesenteric ischemia/reperfusion (I/R). The purpose of the present study was to determine if the nonmetabolizable solute alanine differentially modulates cytoskeletal organization and paracellular small intestinal permeability compared with the metabolizable solutes glucose and glutamine following mesenteric I/R. At laparotomy, rats had jejunal sacs filled with 10 mM glucose, glutamine, alanine, or magnesium sulfate (5 mm, osmotic control) followed by superior mesenteric artery clamping for 60 min and 30 min of reperfusion or sham laparotomy. Jejunum was harvested for evaluation by deconvolution microscopy, fluorescent measurement of F:G actin ratio, or mounted in an Ussing chamber for determination of intestinal permeability. Deconvolution microscopy revealed that the actin cytoskeleton was preserved by enteral glutamine, comparable to shams, but disrupted by enteral alanine. Glucose and controls resulted in comparable disruption, which was less than that with alanine. The F:G actin ratio was highest for glutamine and lowest for alanine; glucose was comparable to controls. Intestinal permeability was highest for alanine and lowest for glutamine, which was comparable to shams. Permeability following glucose and controls was higher than that following glutamine but lower than that following alanine. The nonmetabolizable solute alanine resulted in disruption of the actin cytoskeleton and enhanced intestinal permeability under conditions of mesenteric I/R. The metabolizable solute glutamine was protective under these conditions, whereas glucose exerted minimal effect on the integrity of the cytoskeleton and intestinal permeability. The individual components of enteral diets may differentially modulate intestinal barrier function, which could have important implications when administered to critically injured patients.

Alanine↗
PubMed2004

Hypertonic saline prevents inflammation, injury, and impaired intestinal transit after gut ischemia/reperfusion by inducing heme oxygenase 1 enzyme.

BACKGROUND: Hypertonic saline (HTS) has been shown to modulate the inflammatory response after shock. We have previously demonstrated that heme oygenase-1 (HO-1) induction is protective against gut dysfunction in models of shock-induced gut ischemia/reperfusion (I/R). We therefore hypothesized that HTS prevents gut inflammation, injury, and impaired transit by inducing HO-1 in a model of gut I/R. METHODS: Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then were resuscitated with 4 mL/kg of HTS, an equal volume of lactated Ringer's (LR) solution (4 mL/kg, low volume), or equal salt LR solution (32 mL/kg, high volume) and compared with SMAO alone or shams. A separate group was pretreated with the HO-1 blocker Sn protoporphyrin IX (SNP IX) before SMAO plus HTS. At 6 hours of reperfusion, transit was determined and ileum harvested for HO-1 (anti-inflammatory) and inducible nitric oxide synthase (proinflammatory) immunoreactivity, myeloperoxidase (MPO) activity, and histologic injury. Data are expressed as mean +/- SEM (analysis of variance). RESULTS: Intestinal transit was severely impaired after SMAO (2.5 +/- 0.1), improved with low- and high-volume LR solution (3.2 +/- 0.2 and 3.1 +/- 0.1, not significant), but returned to sham (4.6 +/- 0.2) with HTS (4.8 +/- 0.2). Pretreatment with SNP abrogated this protective effect. Myeloperoxidase activity was significantly increased by SMAO (SMAO, 2.3 +/- 0.3; sham, 0.4 +/- 0.05), lessened by low- and high-volume LR solution (1.5 +/- 0.3 and 1.7 +/- 0.4), but returned to sham levels with HTS (1.0 +/- 0.01). Activity with SNP IX pretreatment was significantly increased (4.04 +/- 0.8). Mucosal injury followed a similar pattern. Inducible nitric oxide synthase was increased by SMAO and low- and high-volume LR solution (0.8 +/- 0.2, 0.8 +/- 0.03, and 0.8 +/- 0.02, respectively; sham, 0.5 +/- 0.02), but significantly reduced by HTS (0.7 +/- 0.02). HO-1 was induced by SMAO and low- and high-volume LR solution (0.33 +/- 0.02, 0.32 +/- 0.03, and 0.37 +/- 0.4, respectively; sham, 0.0 +/- 0.0), but was further increased with HTS (0.49 +/- 0.04). CONCLUSION: HTS resuscitation protects against inflammation, injury, and impaired intestinal transit after gut I/R in part by inducing HO-1. This is a novel mechanism of HO-1 protection.

Animals↗