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Biomedical subjects

T C Fabian

Publications and source records attributed to T C Fabian.

At least 37 records · Page 2Linked to original sources
PubMed2000

Emergency department discharge of patients with a negative cranial computed tomography scan after minimal head injury.

OBJECTIVE: To determine the negative predictive value of cranial computed tomography (CT) scanning in a prospective series of patients and whether hospital admission for observation is mandatory after a negative diagnostic evaluation after minimal head injury (MHI). SUMMARY BACKGROUND DATA: Hospital admission for observation is a current standard of practice for patients who have sustained MHI, despite having undergone diagnostic studies that exclude the presence of an intracranial injury. The reasons for this practice are multifactorial and include the perceived false-negative rate of all standard diagnostic tests, the belief that admission will allow prompt diagnosis of occult injuries, and medicolegal considerations about the risk of early discharge. METHODS: In a prospective, multiinstitutional study during a 22-month period at four level I trauma centers, all patients with MHI were evaluated using the following protocol: a standardized physical and neurologic examination in the emergency department, cranial CT scanning, and then admission for observation. MHI was defined as either a documented loss of consciousness or evidence of posttraumatic amnesia and an emergency department Glasgow Coma Scale score of 14 or 15. Outcomes were measured at 20 hours and at discharge and included clinical deterioration, need for craniotomy, and death. RESULTS: Two thousand one hundred fifty-two consecutive patients fulfilled the study protocol. The CT was interpreted as negative for intracranial injury in 1,788, positive in 217, and equivocal in 119. Five patients with CT scans initially interpreted as negative required intervention. There was one craniotomy in a patient whose CT scan was initially interpreted as negative. This patient had facial fractures that required surgical intervention and elevation of depressed intracranial fracture fragments. The negative predictive power of a cranial CT scan based on the preliminary reading of the CT scan and defined by the subsequent need for neurosurgical intervention in the population fully satisfying the protocol was 99.70%. CONCLUSIONS: Patients with a cranial CT scan, obtained on a helical CT scanner, that shows no intracerebral injury and who do not have other body system injuries or a persistence of any neurologic finding can be safely discharged from the emergency department without a period of either inpatient or outpatient observation. Implementation of this practice could result in a potential decrease of more than 500,000 hospital admissions annually.

Adolescent↗
PubMed2000

Effects of fiberoptic bronchoscopy on intracranial pressure in patients with brain injury: a prospective clinical study.

BACKGROUND: Fiberoptic bronchoscopy (FB) plays an important role in making the diagnosis of nosocomial pneumonia and resolving lobar atelectasis in critically injured trauma patients. It has been shown to be a safe procedure with only occasional complications. However, in patients with head injuries, FB can lead to intracranial hypertension. Sustained increases in intracranial pressure (ICP) leads to poor outcome in these patients. Because of this, a prospective study was done not only to assess the effect of FB on ICP and cerebral perfusion pressure (CPP) in patients with brain injuries, but also to identify a regimen of sedation and anesthesia that could prevent significant increases in ICP during FB. METHODS: Twenty-six FB were performed in 23 patients with ICP monitors or ICP monitors and ventriculostomy drains in place for Glasgow Coma Scale score < 8 or management of postcraniotomy trauma. FB was performed to aid in the diagnosis of nosocomial pneumonia or to aid in resolving lobar atelectasis. Before FB, all patients received a standard anesthetic regimen consisting of vecuronium (10 mg), morphine sulfate (4 mg), and midazolam (2.5 mg). Patients with diminished cranial compliance, defined as ICP > 10 mm Hg, also received a nebulizer treatment of 3 mL of 4% lidocaine before FB. All patients were preoxygenated with FIO2 = 1.0 for 10 minutes. Intracranial pressure, mean arterial pressure, and CPP were monitored continuously throughout the procedure. These same variables were also recorded at baseline and at 2-minute intervals during the procedure. The time to return to baseline ICP was also recorded. RESULTS: The mean ICP at baseline (immediately before FB) was 12.6 mm Hg. After introduction of the bronchoscope, the ICP rapidly increased in 21 procedures (81%) and the mean highest ICP was 38.0 mm Hg. There was also a concomitant increase in mean arterial pressure such that there was no substantial change in CPP. The mean lowest CPP was 73.1 mm Hg. The average time for return of ICP to baseline was 13.9 minutes. In the subgroup of patients with ICP > 10, attempting to blunt the tracheal stimulation by anesthetizing the trachea with 4% nebulized lidocaine did not seem to be successful. The mean highest ICP in this subgroup was 41.8 mm Hg. The CPP changed in a similar manner, as the mean lowest CPP was 74.0 mm Hg. The mean time to return to baseline was 12.5 minutes. No patient had acute neurologic deterioration secondary to FB. CONCLUSIONS: Although FB is an important procedure in the pulmonary care of head injured patients, it produces substantial, but transient, increases in ICP and should be used with caution in patients with diminished cranial compliance. Sedation, analgesia, paralysis, and topical tracheal anesthesia did not completely prevent the rise in ICP. Although no acute deterioration in condition occurred, secondary brain injury caused by localized cerebral ischemia is certainly possible. Because of the substantial increases in ICP, herniation may be precipitated in an occasional patient. Further study is needed to identify a regimen that will confer protection.

Adolescent↗
PubMed2000

Blunt bowel and mesenteric injuries: the role of screening computed tomography.

BACKGROUND: Early generation scanners have demonstrated poor sensitivity detecting blunt bowel/mesenteric injuries (BBMI). This study was aimed at determining the accuracy and role of helical scanners in BBMI. METHODS: Retrospective chart review of patients with BBMI, or computed tomographic scans suspicious of BBMI, from August of 1995 to December of 1998. RESULTS: One hundred of 8,112 scans (1.2%) were suspicious of BBMI. Of these suspicious scans, 53 patients had BBMI (true positive-TP) and 47 patients did not (false positive-FP). Seven patients with negative scans had BBMI (false negative-FN). Computed tomography contributed toward early surgery in 77% of patients who may have been delayed. Six patients developed intra-abdominal abscess. The abscess group had a significantly longer time interval from injury to surgery. Multiple findings were seen in 57% of true positive scans, whereas in 13% of false positive scans (p < 0.0001). An algorithm for management of BBMI is presented. CONCLUSION: Helical scanners have high accuracy in detecting BBMI. Single versus multiple findings are useful in managing these injuries.

Abdominal Abscess↗
PubMed2000

Resuscitation of severe chest trauma with four different hemoglobin-based oxygen-carrying solutions.

BACKGROUND: The purpose of this study was to test whether polynitroxylation (PN) improved the therapeutic profile of hemoglobin-based oxygen-carrying compounds (HBOCs) that were unpolymerized (alphaalphaHb) or 70% polymerized (polyHb) in a clinically relevant model that combines pulmonary injury and reperfusion. To our knowledge, four different HBOC formulations have never been compared in the same trauma model. METHODS: Anesthetized, ventilated swine (n = 45) received a unilateral lung contusion + 25% hemorrhage. After 60 minutes, 250 mL of either PNalphaalphaHb (n = 5), alphaalphaHb (n = 10), PNpolyHb (n = 6), polyHb (n = 5), or normal saline (NaCl, n = 10) was administered for 20 minutes, followed by standard crystalloid resuscitation for 30 minutes, and supplemental crystalloid as required for 6 hours to maintain heart rate <100 beats/min and mean arterial pressure >70 mm Hg. RESULTS: Nine of 45 deaths occurred before resuscitation. Survival time was 395 minutes with NaCl versus 303 minutes with alphaalphaHb (p = 0.03) or 238 minutes with PNalphaalphaHb (p = 0.04). With both polymerized HBOCs, survival was 480 minutes (polyHb vs. alphaalphaHb, p = 0.005; PNpolyHb vs. PNalphaalphaHb, p = 0.006). All HBOCs were pressors (all p < 0.05) and all reduced the supplemental fluid required to maintain systemic hemodynamics during resuscitation (all p < 0.05). By 90 minutes postresuscitation, cardiac index was 112% of baseline with NaCl (p < 0.02), but was 78% with alphaalphaHb (p = not significant), 63% with PNalphaalphaHb (p < 0.01), 79% with PNpolyHb (p < 0.01), and 67% with polyHb p < 0.02). Relative to NaCI, no HBOC altered trauma-induced neutrophilia, thrombocytopenia, or the trauma-induced increases in bronchoalveolar lavage protein or bronchoalveolar lavage neutrophils. CONCLUSION: After resuscitation from chest trauma, we observed the following: (1) all HBOCs reduced fluid requirements and increased right and left ventricular afterload versus NaCl, which further compromised an already marginal cardiac performance; (2) mortality was less with polyHbs relative to alphaalphaHb, but the pressor action was unchanged; (3) the pressor action was less with polynitroxylated compounds relative to the unmodified HBOC, but this chemical modification had no effect on mortality; and (4) the pressor action of HBOCs must be attenuated by strategies other than polymerization or polynitroxylation for these compounds to be safe, effective resuscitants in humans.

Animals↗
PubMed2000

Endogenous adenosine and secondary injury after chest trauma.

BACKGROUND: No previous studies have examined actions of adenosine or related compounds after blunt chest trauma, but we have shown that the prototype adenosine-regulating agent, acadesine (aminoimidazole carboxamide ribonucleotide [AICAR]), has multiple favorable anti-inflammatory actions after other forms of trauma, ischemia, hemorrhage, and sepsis; and that a progressive inflammatory response in the contralateral (uninjured) lung after unilateral blunt chest trauma is caused (in part) by activation and sequestration of circulating leukocytes (white blood cells [WBCs]). Thus, we hypothesized that AICAR would ameliorate WBC-dependent, secondary pathophysiologic changes after blunt chest trauma. METHODS: Mongrel pigs (28+/-1 kg, n = 21) were anesthetized, mechanically ventilated, and injured on the right chest (pulmonary contusion) with a captive bolt gun. Either AICAR (1 mg/kg + 0.2 mg/kg/min) or its saline vehicle were administered for a 12-hour period, beginning 15 minutes before injury. RESULTS: Injury caused a three- to fourfold increase in bronchoalveolar lavage (BAL) WBC counts, 10- to 20-fold increases in BAL protein, and 200% increases in lung edema as measured by wet-dry ratio (all p < 0.05), in both the injured (right) and the noninjured (left) lungs. With AICAR versus saline, BAL WBC counts, lung myeloperoxidase levels, and systemic hemodynamics were similar. However, the increases in BAL protein were attenuated by 30% to 50% (p < 0.14, NS) and edema was reduced (p < 0.05) in both lungs. Furthermore, oxygenation, hypercapnia, acidosis (all p < 0.05), and survival were improved (9 of 10 vs. 4 of 11, p < 0.04). CONCLUSION: Pretreatment with AICAR before experimental pulmonary contusion ameliorates the trauma-induced destruction of the alveolar capillary membrane, and attenuates the delayed secondary injury in the contralateral uninjured lung, by a mechanism that may be independent of leukocytes. Endogenous adenosine could have a role in the pathophysiologic response after blunt chest injury, with potential sites of action including the endothelium and alveolar macrophage. Adenosine-regulating agents may have therapeutic potential after blunt chest injury, but further studies are needed in clinically relevant models, with administration begun at the time of resuscitation.

Acidosis↗
PubMed2000

Effects of a novel antioxidant during resuscitation from severe blunt chest trauma.

Previous work suggests that neutrophils (PMNs) and/or prostaglandins might mediate the progressive respiratory failure after severe pulmonary contusion. Since reactive oxygen metabolites are closely associated with both these factors, we examined the actions of a novel antioxidant after swine received a unilateral injury followed by 25% hemorrhage. An infusion (2mL/kg/h intravenously x 6 h) of either polynitroxylated 5% Dextran + Tempol (PND, n = 9), 5% Dextran (D, n = 6), or lactated Ringers (LR, n = 13) was begun 60 min post-injury to mimic 'pre-hospital resuscitation.' After 15 min, standard resuscitation was initiated (3x shed blood as LR in 30 min) plus further LR for 6 h to maintain hemodynamics. The total LR requirement was lower with PND (1,772+/-267 mL) versus D (3,040+/-689, P = 0.0563) or LR (4145+/-398, P = 0.0005). The ipsilateral bronchoalveolar lavage (BAL) PMN count with PND (8+/-2 x 10(5)/mL), was not different from its baseline (P = 0.131), but the counts with D (16+/-3) and LR (17+/-4) were both higher than their baselines (P = 0.0184 and 0.0431). Similarly, BAL protein with PND (1,560+/-350 mg %) was not elevated from its baseline (P = 0.0721), but the values with D (2,560+/-498) and LR (2,474+/-899) were both higher than their baselines (P = 0.0169 and 0.0325). In the contralateral (uninjured) lung, the effects were similar, but the increases were less for PMNs (8+/-2 versus 10+/-2 or 14+/-4 x 10(5)/mL) and for protein (609 +/-153 versus 1,955+/-671 or 1486+/-357 mg %). Despite these significant BAL changes, there was no obvious improvement in cardiopulmonary dysfunction. Thus oxidants probably have some role in the pathogenic mechanism of progressive secondary injury after thoracic trauma, but further work is needed to determine the therapeutic potential of antioxidants because no clinical improvement was detected.

Animals↗
PubMed2000

An objective analysis of process errors in trauma resuscitations.

OBJECTIVE: A computer-based system to apply trauma resuscitation protocols to patients with penetrating thoracoabdominal trauma was previously validated for 97 consecutive patients at a Level 1 trauma center by a panel of the trauma attendings and further refined by a panel of national trauma experts. The purpose of this article is to describe how this system is now used to objectively critique the actual care given to those patients for process errors in reasoning, independent of outcome. METHODS: A chronological narrative of the care of each patient was presented to the computer program. The actual care was compared with the validated computer protocols at each decision point and differences were classified by a predetermined scoring system from 0 to 100, based on the potential impact on outcome, as critical/noncritical/no errors of commission, omission, or procedure selection. RESULTS: Errors in reasoning occurred in 100% of the 97 cases studied, averaging 11.9/case. Errors of omission were more prevalent than errors of commission (2. 4 errors/case vs 1.2) and were of greater severity (19.4/error vs 5. 1). The largest number of errors involved the failure to record, and perhaps observe, beside information relevant to the reasoning process, an average of 7.4 missing items/patient. Only 2 of the 10 adverse outcomes were judged to be potentially related to errors of reasoning. CONCLUSIONS: Process errors in reasoning were ubiquitous, occurring in every case, although they were infrequently judged to be potentially related to an adverse outcome. Errors of omission were assessed to be more severe. The most common error was failure to consider, or document, available relevant information in the selection of appropriate care.

Abdominal Injuries↗
PubMed2000

Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

Adult↗
PubMed2000

Oxandrolone in trauma patients.

STUDY OBJECTIVE: To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Level 1 trauma center in a university teaching hospital. PATIENTS: Sixty-two patients requiring enteral nutrition, 60 of whom completed the study. INTERVENTION: Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days. MEASUREMENTS AND MAIN RESULTS: Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients were assessed daily for metabolic and infectious complications. The two groups were similar for demographics and dosage of enteral nutrition. Measurement of total urinary nitrogen at study entry showed both groups to be highly catabolic (oxandrolone 17.2 +/- 4.9, placebo 19.1 +/- 10.8 g/day, NS). On days 7 and 10, total urinary nitrogen increased in both groups; however, there was no significant difference between groups. Nitrogen balance was negative throughout the study in each group. Body cell mass decreased slightly in both groups over the study period. Prealbumin serum concentrations increased significantly in both groups at day 10 and study exit compared with study entry. The groups did not differ significantly for length of hospital stay (oxandrolone 30.8 +/- 17.9, placebo 27.0 +/- 25.7 days), length of intensive care unit stay (oxandrolone 17.1 +/- 7.8, placebo 15.5 +/- 9.7 days), and frequency of pneumonia or sepsis (oxandrolone 48, placebo 43 episodes). CONCLUSION: Oxandrolone 20 mg/day does not have obvious benefit in nutritional and clinical outcomes during the first month after multiple trauma.

Adult↗
PubMed2000

Empiric therapy for pneumonia in the surgical intensive care unit.

Empiri c therapy of ventilator-associated pneumonia (VAP) in surgical patients should be based on intensive care unit (ICU)-specific surveillance data, because microbial flora patterns vary widely between geographic regions as well as within hospitals. Surgical ICUs have higher VAP rates than other units. Data from the National Nosocomial Infection Surveillance (NNIS) System report Pseudomonas aeruginosa and Staphylococcus aureus to be the most frequent isolates (each 17.4%). Data from the NNIS documents high resistance patterns in ICUs compared with hospitals at large, as well as unit-specific patterns. VAP risk factors for surgical patients include thoracoabdominal surgery, altered level of consciousness, advanced age, diabetes mellitus, malnutrition, chronic obstructive pulmonary disease, and prior antibiotic administration. Promising prevention strategies include restricting ventilator circuit changes, in-line heat moisture exchange filters, semi-recumbant positioning, and continuous subglottic aspiration. Pharmacodynamics should be considered when choosing antibiotic regimens. Postantibiotic effect and time-dependent versus concentration-dependent killing should be studied in clinical trials. Current guidelines for choosing regimens have been well developed by the American Thoracic Society.

Clinical Trials as Topic↗
PubMed1999

Traumatic rupture of the aortic isthmus: program of selective management.

Two hypotheses were investigated: (1) helical computed tomography (CT) of the chest on victims of decelerating trauma can yield a diagnosis of, or "rule out," a traumatic rupture of the aorta (TRA) without the need for an aortogram; and (2) selective delay of aortic repair can be safely accomplished through a medical management protocol. Screening helical CT examinations were done on 6169 victims of blunt thoracic trauma; 47 were found to have TRA; in 8, indirect but nondiagnostic findings not clarified by an aortogram led to surgical exploration. The sensitivity of helical CT was higher than that of aortograms, and a "normal" helical CT scan was never associated with a proved TRA. It is estimated that the use of helical CT has resulted in at least a 40% to 50% decrease in the need for aortograms, in addition to yielding rapid, noninvasive valuable information about other injuries. Drugs (beta-blockers +/- vasodilators) to decrease the stress in the aortic wall were used in 93 patients when the diagnosis was suspected and were continued as necessary through the evaluation, stabilization, and until the aorta was cross-clamped at operation. Elective, delayed operation was done between 2 days and 25 months in 15 patients who were deemed to be excessive risks for emergency aortic repair; there were 2 deaths (13. 3%). Eleven patients never had aortic repair. No patient maintained on this protocol, whether repaired emergently, electively, or not at all, developed free rupture of the periaortic hematoma and death from TRA.

Accidents, Traffic↗
PubMed1999

Prognostic value of blood lactate, base deficit, and oxygen-derived variables in an LD50 model of penetrating trauma.

OBJECTIVE: To determine whether blood lactate, base deficit, or oxygen-derived hemodynamic variables correlate with morbidity and mortality rates in a clinically-relevant LD50 model of penetrating trauma. DESIGN: Prospective, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized, mechanically-ventilated mongrel pigs (30+/-2 kg, n = 29). INTERVENTIONS: A captive bolt gun delivered a penetrating injury to the thigh, followed immediately by a 40% to 60% hemorrhage. After 1 hr, shed blood and supplemental crystalloid were administered for resuscitation. MEASUREMENTS AND MAIN RESULTS: After penetrating injury, 50.7+/-0.3% hemorrhage (range 50% to 52.5%), and a 1-hr shock period, seven of 14 animals died, compared with six of six animals after 55% to 60% hemorrhage, and 0 of nine animals after < or =47.5% hemorrhage. Only two of 13 deaths occurred during fluid resuscitation. At the LD50 hemorrhage, peak lactate concentration and base deficit were 11.2+/-0.8 mM and 9.3+/-1.5 mmol/L, respectively, and minimum mixed venous oxygen saturation, systemic oxygen delivery, and systemic oxygen consumption were 33+/-5%, 380+/-83 mL/min/kg, and 177+/-35 mL/min/kg, respectively. For comparison, baseline preinjury values were 1.6+/-0.1 mM, -6.7+/-0.6 mmol/L, 71+/-3%, 2189+/-198 mL/min/kg, and 628+/-102 mL/min/kg, respectively. Of all the variables, only lactate was significantly related to blood loss before and after fluid resuscitation in the 16 survivors. However, r2 values were relatively low (.20 to .50), which indicates that only a small fraction of the hyperiactacidemia was directly related to tissue hypoperfusion. In the whole population of survivors and nonsurvivors, both lactate and base deficit (but none of the oxygen-derived variables) correlated with blood loss. CONCLUSIONS: Arterial lactate is a stronger index of blood loss after penetrating trauma than base deficit or oxygen-derived hemodynamic variables. The reliability of arterial lactate depends on several factors, such as the time after injury, the proportion of survivors and nonsurvivors in the study population, and on factors other than tissue hypoxia.

Analysis of Variance↗
PubMed1999

Acadesine during fluid resuscitation from shock and abdominal sepsis.

OBJECTIVE: To determine properties of acadesine, the prototype adenosine regulating agent, in an experimental model in which abdominal sepsis is superimposed onto hemorrhagic shock. DESIGN: Randomized, blinded animal study. SETTING: University-based animal research facility. SUBJECTS: Twenty-eight anesthetized mongrel pigs (35.5 +/- 1.1 kg). INTERVENTIONS: The cecum was ligated and punctured to produce abdominal sepsis. To produce hemorrhagic shock, 45% to 47% of the estimated blood volume was withdrawn. After 1 hr, shed blood plus supplemental crystalloid (twice the shed blood volume) plus either acadesine (5 mg/kg bolus + 1 mg/kg x 60 min, n = 10) or its vehicle (n = 10) was administered. All animals were awakened and observed for 48 hrs. At 48 hrs, cardiac function, bacterial cultures from the septic focus, and inflammatory changes in the abdomen were quantified. MEASUREMENTS AND MAIN RESULTS: After resuscitation with acadesine vs. vehicle, we observed the following: a) arterial blood pressure and cardiac filling pressures were similar but cardiac index, systemic oxygen delivery, and systemic oxygen consumption were increased; b) plasma lactate was higher, systemic vascular resistance was lower, but ileal mucosal blood flow was not measurably altered; c) lipopolysaccharide-evoked tumor necrosis factor production in whole blood ex vivo was reduced; d) in those animals that survived 48 hrs (10/10 vs. 8/10), sepsis-induced cardiac depression, amount of free intraperitoneal fluid, extra abscess inflammatory reaction, abscess wall formation, abscess bacterial counts, and peritoneal bacterial counts, were all similar, but blood bacterial counts were higher. CONCLUSIONS: Fluid resuscitation with acadesine produced no adverse hemodynamic consequences and probably improved washout of metabolites from the reperfused microcirculation in sites other than the small intestine or heart. Taken together, these observations suggest that adenosine regulating agents might have therapeutic potential during fluid resuscitation from trauma. However, at least in these extreme conditions, the acute salutary effects of acadesine were probably overwhelmed by polymicrobial sepsis. Further studies must determine whether supplemental adjuvants to boost host defense during recovery from trauma will optimize adenosine-based resuscitation solutions.

Aminoimidazole Carboxamide↗
PubMed1999

Early and late acute respiratory distress syndrome: two distinct clinical entities.

BACKGROUND: Despite numerous advances in surgical critical care and ventilatory management, mortality rates for acute respiratory distress syndrome (ARDS) have remained relatively constant. Pressure-limited and non-pressure-limited ventilatory techniques have been advocated with disparate results. We hypothesized that there are two forms of ARDS, which may account for the conflicting clinical reports. METHODS: Patients with posttraumatic ARDS were identified and reviewed. ARDS was defined as PaO2/FiO2 ratio less than 200 with diffuse bilateral infiltrates on chest radiograph and no congestive heart failure. Patients were analyzed relative to injury mechanism, transfusions, fluid balance, presence of pneumonia (defined as > or =10(5) colony-forming units/mL in bronchoalveolar lavage effluent), and outcome. All were managed with a non-pressure-limited strategy. RESULTS: During a 5.5-year period, 178 patients with posttraumatic ARDS were identified. Mean Injury Severity Score and age were 29 and 40 years, respectively. Patients were stratified by time of ARDS diagnosis. Eighty-two patients (46%) had early ARDS (within 48 hours after admission), and 96 patients (54%) had late ARDS (>48 hours between admission and diagnosis). There were no differences in Injury Severity Score, but the late group was significantly older. The early ARDS group was characterized by profound hemorrhagic shock and had significant differences from the late group in incidence of penetrating injury (30 vs. 10%; p<0.001), admission base deficit (-7.7 vs. -4.2 mEq/L; p<0.001), 48-hour transfusions (19.7 vs. 9.4; p<0.0001), initial 5-day fluid balance (19.9 vs. 10.1 L; p<0.0001), and initial PaO2/FiO2 (121 vs. 141; p<0.007). Pneumonia before ARDS was significantly associated with late ARDS (38 vs. 9%; p<0.001). ARDS-related mortality was primarily caused by hemorrhagic shock in the early group and progressive multiple organ failure in the late group. CONCLUSION: There are two distinct forms of posttraumatic ARDS. Early ARDS is characterized by hemorrhagic shock with capillary leak. Late ARDS frequently follows pneumonia and is associated with multiple system injury. Further studies should differentiate between these two distinct syndromes.

Adolescent↗
PubMed1999

Prostanoids: early mediators in the secondary injury that develops after unilateral pulmonary contusion.

BACKGROUND: We have previously shown a sequence of events after unilateral pulmonary contusion that suggests the release of blood-borne prostanoid mediators and that culminates in refractory bilateral pulmonary failure. PURPOSE: To determine the role of platelet-derived thromboxane and endothelial-derived prostacyclin in the primary and secondary injury after unilateral blunt chest trauma, and to determine whether pretreatment with the cyclooxygenase inhibitor indomethacin alters the progression of secondary injury. METHODS: Anesthetized, ventilated (FIO2 = 0.50) pigs received a unilateral, blunt injury to the right thorax (n = 20) or sham injury (n = 5) and were monitored for 24 hours. Either indomethacin (5 mg/kg i.v.; n = 10) or its saline vehicle (n = 10) were administered 15 minutes before injury. Serial bronchoalveolar lavages of each lung were analyzed for protein and neutrophil (polymorphonuclear neutrophil (PMN)) content. RESULTS: Contusion caused profound hypoxemia; PaO2 partially recovered within 1 hour of injury to 50% of baseline. Thereafter, worsening hypoxemia required positive end-expiratory pressure. With indomethacin compared with vehicle, PaO2 was higher at any given level of positive end-expiratory pressure (p < 0.05). There was an early increase in serial bronchoalveolar lavage protein on the injured side (peak at 2 hours), with a delayed pulmonary capillary leak on the contralateral side (peak at 6 hours), which correlated with increasing PMN infiltration; this was reduced by 40 to 60% with indomethacin (p < 0.05). Thromboxane peaked within 1 hour after contusion at 800% baseline, then fell off rapidly. This peak preceded the maximal increase in permeability and was completely blocked by indomethacin. Prostacyclin slowly rose to 300% baseline by 3 hours and remained elevated; this change was blocked by indomethacin for 18 hours. CONCLUSIONS: Contusion of the right thorax induced a delayed pulmonary capillary leak in the left lung, which reflects a progressive secondary inflammatory response. Elevations in thromboxane and prostacyclin preceded progressive bilateral PMN infiltration. Indomethacin blocked thromboxane and prostacyclin and attenuated, but did not prevent, the progression to pulmonary failure. Overall, these data suggest that prostanoids are released soon after unilateral contusion and initiate an inflammatory response in both lungs that is sustained by PMN infiltration.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Secondary abdominal compartment syndrome: an underappreciated manifestation of severe hemorrhagic shock.

OBJECTIVE: Abdominal compartment syndrome (ACS) has multiple well-described etiologies, but almost no attention has focused on ACS in the absence of abdominal injury. This study describes a secondary ACS that occurs after severe hemorrhagic shock with no evidence of abdominal injury. METHODS: The trauma registry at a Level I trauma center was reviewed for a 13-month period beginning July 1, 1997. RESULTS: During the study period, there were 46 of 1,216 intensive care unit admissions (4%) who required laparotomy and mesh closure of the abdominal wall because of visceral edema. In that subgroup, six patients (13% of mesh closures, 0.5% intensive care unit admissions) had hemorrhagic shock (5/1, blunt/penetrating trauma) but no evidence of intra-abdominal injury. Associated extremity compartment syndrome developed in two of six (33%). Overall mortality was four of six (67%), secondary to sepsis (n = 3), and head injury (n = 1). Time from admission to decompression averaged 3 hours in survivors and 25 hours in nonsurvivors (overall average = 18+/-9 hours). Resuscitation volume before abdominal decompression averaged 19+/-5 liters of crystalloid and 29+/-10 units of packed red blood cells. Bladder pressure averaged 33+/- 3 mm Hg. Decompression significantly improved peak inspiratory pressure (p < 0.003) and base deficit (p < 0.003). CONCLUSION: ACS can occur with no abdominal injury; The incidence of secondary ACS was 0.5% in this cohort trauma intensive care unit patients, so it probably occurs more frequently than is currently appreciated. Because survivors were decompressed 20 hours before nonsurvivors, early recognition might improve outcomes. On the basis of these observations, we recommend that bladder pressures should be routinely checked and acted on appropriately when resuscitation volumes approach 10 liters of crystalloid or 10 units of packed red cells.

Abdomen↗
PubMed1999

Mediator-dependent secondary injury after unilateral blunt thoracic trauma.

The pathophysiologic sequence leading to respiratory failure after chest trauma can be an inevitable consequence of the primary injury or a secondary, mediator-driven inflammatory process. To distinguish between these alternatives, a simple cross-transfusion experiment was performed. A captive bolt gun injured the chest of anesthetized pigs that were mechanically ventilated with FiO2 = .21, .50, or .50 plus indomethacin (5 mg/kg intravenous; 15 min before injury). Tube thoracostomy immediately followed. After 30 min, blood from these injured donors was transfused into three matched groups of naive recipients (n = 8, 6, and 4, respectively) for a 33% exchange transfusion. Two control groups received blood from uninjured donors with tube thoracostomies only (FiO2 = .21, n = 7; FiO2 = .50, n = 10). Within 15-30 min after transfusion, in recipients from injured donors versus controls, lung compliance was decreased 20%, stroke volume and cardiac output were decreased 50%, and pulmonary vascular resistance was increased >300% (all p < .05). These changes recovered to baseline within 60-90 min. The stable metabolite of thromboxane A2, thromboxane B2, increased >500% in plasma within 15 min and remained elevated for >120 min. All responses were similar at 21 % or 50% O2, which suggests that hypoxia per se is not a cause of mediator production. All responses were eliminated by indomethacin. By 24 h, histologic changes included atelectasis in 3/3 recipients from injured donors versus 0/3 recipients from uninjured donors. We conclude that 1) blunt chest trauma releases blood borne mediators, including prostanoids; 2) these mediators can cause secondary cardiopulmonary changes in naive recipients similar to those produced by chest trauma; 3) the progression to trauma-induced respiratory failure is multifactorial; 4) early pharmacologic intervention, rather than supportive care alone, may benefit some victims of severe chest trauma.

Animals↗