Biomedical subjects

M A Croce

Publications and source records attributed to M A Croce.

At least 37 records · Page 2Linked to original sources

PubMed1999

Construction and in vitro functional evaluation of a low-density lipoprotein receptor/transferrin fusion protein as a therapeutic tool for familial hypercholesterolemia.

A cDNA sequence encoding a soluble form of the human low-density lipoprotein receptor (LDL-R) was produced by RT-PCR amplification. This form of the receptor contains the N-terminal cysteine-rich domain, the EGF homology domain, and the serine/threonine-rich domain, but lacks the membrane anchor as well as the cytoplasmic domain. By the same technical approach a cDNA sequence encoding rabbit transferrin was generated. In-frame fusion of the two cDNAs produced a sequence encoding a chimeric protein potentially capable of binding LDL on the N-terminal side and the transferrin receptor on the C-terminal side. It was expected that LDL bound to the chimeric protein could be internalized, targeted to an acidic compartment, and processed through the pathway of the transferrin receptor. Cells transfected with the LDL-R/transferrin cDNA translate, glycosylate, and secrete the corresponding protein in the culture medium. The secreted protein binds LDL in a ligand-blotting experiment. Finally, the chimeric protein mediates the binding and internalization of LDL in mutant cells lacking the LDL receptor. In fact, Watanabe rabbit fibroblasts, incubated with the chimeric protein show a fourfold increase in LDL binding, a fivefold increase in LDL internalization, and a sixfold increase in LDL degradation, with respect to unincubated fibroblasts.

Animals↗

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

Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial.

OBJECT: Sedation regimens for head-injured patients are quite variable. The short-acting sedative-anesthetic agent propofol is being increasingly used in such patients, yet little is known regarding its safety and efficacy. In this multicenter double-blind trial, a titratable infusion of 2% propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients. In both groups, other standard measures of controlling intracranial pressure (ICP) were also used. METHODS: Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol: 23 patients in the propofol group (mean time of propofol usage 95+/-87 hours) and 19 patients in the morphine group (mean time of morphine usage 70+/-54 hours). There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group: patient age older than 55 years (30.4% compared with 10.5%, p < 0.05), initial Glasgow Coma Scale scores of 3 to 5 (39.1% compared with 15.8%, p < 0.05), compressed or absent cisterns on initial computerized tomography scanning (78.3% compared with 57.9%, p < 0.05), early hypotension and/or hypoxia (26.1% compared with 10.5%, p = 0.07). During treatment there was a trend toward greater use of vasopressors in the propofol group. However, the mean daily ICP and cerebral perfusion pressure were generally similar between groups and, on therapy Day 3, ICP was lower in the propofol group compared with the morphine group (p < 0.05). Additionally, there was less use of neuromuscular blocking agents, benzodiazepines, pentobarbital, and cerebrospinal fluid drainage in the propofol group (p < 0.05). At 6 months postinjury, a favorable outcome (good recovery or moderate disability) was observed in 52.1% of patients receiving propofol and in 47.4% receiving morphine; the mortality rates were 17.4% and 21.1%, respectively. Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes. There were no significant differences between groups in terms of adverse events. CONCLUSIONS: Despite a higher incidence of poor prognostic indicators in the propofol group, ICP therapy was less intensive, ICP was lower on therapy Day 3, and long-term outcome was similar to that of the morphine group. These results suggest that a propofol-based sedation and an ICP control regimen is a safe, acceptable, and, possibly, desirable alternative to an opiate-based sedation regimen in intubated head-injured patients.

Adult↗

PubMed1999

Granulocyte colony-stimulating factor and neutrophil-related changes in local host defense during recovery from shock and intra-abdominal sepsis.

BACKGROUND: We have reported that treatment with exogenous granulocyte colony-stimulating factor (G-CSF) improves abscess localization and reduces mortality without aggravating neutrophil (PMN)-mediated reperfusion injury in a model of septic abdominal trauma. The purpose of this study was to determine actions of G-CSF on PMN function in the peritoneum. METHODS: Anesthetized swine were pretreated with broad-spectrum antibiotics and underwent cecal ligation and incision and 35% hemorrhage (trauma). After 1 hour they were resuscitated with shed blood, crystalloid, and either G-CSF (n = 10) or saline solution vehicle (n = 9). The animals were observed for 72 hours. RESULTS: After trauma, saline solution treatment increased PMN infiltration into the peritoneum within 2 hours (P = .035), increased peritoneal PMN elastase production (i.e., cytotoxicity) by 24 hours (P = .004), and decreased adherence of peritoneal PMNs to an artificial substrate from 4 to 72 hrs (P = .043). The mean autopsy score was 7.0 +/- 0.5. With G-CSF treatment peritoneal neutrophilia was enhanced (maximum 48 hours, P = .002) and PMN cytotoxicity was augmented and delayed (maximum 48 hours, P = .004). Despite these changes, adherence of peritoneal PMNs was not significantly changed and there was no evidence for PMN-mediated damage in the lung as judged by bronchoalveolar lavage protein, bronchoalveolar lavage PMNs, lung tissue myeloperoxidase, or histologic changes. The mean autopsy score was improved to 4.1 +/- 0.3 (P < .001). CONCLUSIONS: G-CSF in resuscitation fluids improved localization of an intra-abdominal septic focus by increased production of circulating PMNs, increased PMN extravasation into the peritoneal cavity, and increased PMN cytotoxicity at the abdominal septic focus, without exaggerating PMN-dependent reperfusion injury in the lung. Therefore these data further support the idea that G-CSF in resuscitation fluids might reduce septic complications in the multiply injured trauma patient.

Animals↗

PubMed1998

Prospective study of blunt aortic injury: helical CT is diagnostic and antihypertensive therapy reduces rupture.

OBJECTIVE: There were two aims of this study. The first was to evaluate the application of helical computed tomography of the thorax (HCTT) for the diagnosis of blunt aortic injury (BAI). The second was to evaluate the efficacy of beta-blockers with or without nitroprusside in preventing aortic rupture. SUMMARY BACKGROUND DATA: Aortography has been the standard for diagnosing BAI for the past 4 decades. Conventional chest CT has not proven to be of significant value. Helical CT scanning is faster and has higher resolution than conventional CT. Retrospective studies have suggested the efficacy of antihypertensives in preventing aortic rupture. METHODS: A prospective study comparing HCTT to aortography in the diagnosis of BAI was performed. A protocol of beta-blockers with or without nitroprusside was also examined for efficacy in preventing rupture before aortic repair and in allowing delayed repair in patients with significant associated injuries. RESULTS: Over a period of 4 years, 494 patients were studied. BAI was diagnosed in 71 patients. Sensitivity was 100% for HCTT versus 92% for aortography. Specificity was 83% for HCTT versus 99% for aortography. Accuracy was 86% for HCTT versus 97% for aortography. Positive predictive value was 50% for HCTT versus 97% for aortography. Negative predictive value was 100% for HCTT versus 97% for aortography. No patient had spontaneous rupture in this study. CONCLUSIONS: HCTT is sensitive for diagnosing intimal injuries and pseudoaneurysms. Patients without direct HCTT evidence of BAI require no further evaluation. Aortography can be reserved for indeterminate HCTT scans. Early diagnosis with HCTT and presumptive treatment with the antihypertensive regimen eliminated in-hospital aortic rupture.

Adrenergic beta-Antagonists↗

PubMed1998

Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study.

OBJECTIVE: This prospective trial examined the efficacy of using bronchoalveolar lavage (BAL) for the diagnosis of pneumonia (PN) and the utility of Gram's stain (GS) for dictating empiric therapy. SUMMARY BACKGROUND DATA: Posttraumatic nosocomial PN remains a significant cause of morbidity and mortality. However, its diagnosis is elusive, especially in multiply injured patients. The systemic inflammatory response syndrome of fever, leukocytosis, and a hyperdynamic state is common in trauma patients, especially patients with pulmonary contusion. Bronchoscopy with BAL with quantitative cultures of the lavage effluent may distinguish between PN and systemic inflammatory response syndrome, and GS of the lavage effluent may guide empiric therapy before quantitative culture results. METHODS: Mechanically ventilated trauma patients with a clinical diagnosis of PN (fever, leukocytosis, purulent sputum, and new or changing infiltrate on chest radiograph) underwent bronchoscopy with BAL. Effluent was sent for GS and quantitative cultures. The diagnostic threshold for PN was > or =10(5) colony-forming units (CFU)/mL, and antibiotics were continued. Antibiotics were stopped for < 10(5) CFU/mL and the diagnosis of systemic inflammatory response syndrome was made. Causative organisms for PN were compared to GS. RESULTS: Over a 2-year period, 232 patients underwent 443 bronchoscopies with BAL (71% men, 29% women; mean age, 41). The mean injury severity score was 30. Sixty percent of the patients had pulmonary contusion, and 59% were cigarette smokers. The overall incidence of PN was 39% and was no different regardless of the number of BALs a patient had. The false-negative rate of BAL was 7%. GS identified gram-positive organisms in 80% of patients with gram-positive PN and 40% of patients with gram-negative PN. GS identified gram-negative organisms in 52% of patients with gram-positive PN and 77% with gram-negative PN. The duration of the intensive care unit stay relative to the timing of BAL was beneficial for guiding empiric therapy. BAL in week 1 primarily identified Haemophilus influenzae and gram-positive organisms; Acinetobacter sp. and Pseudomonas sp. were more common after week 1. CONCLUSIONS: Bronchoscopy with BAL is an effective method to diagnose PN and avoids prolonged, unnecessary antibiotic therapy. Empiric therapy should be adjusted to the duration of the intensive care unit stay because the causative bacteria flora changes over time. GS of BAL effluent correlates poorly with quantitative cultures and is not reliable for dictating empiric therapy.

Adult↗

PubMed1998

Granulocyte colony-stimulating factor improves host defense to resuscitated shock and polymicrobial sepsis without provoking generalized neutrophil-mediated damage.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. METHODS: Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). RESULTS: Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. CONCLUSIONS: Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.

Animals↗

PubMed1998

Improved success in nonoperative management of blunt splenic injuries: embolization of splenic artery pseudoaneurysms.

OBJECTIVES: By using abdominal computed tomographic scans in the evaluation of blunt splenic trauma, we previously identified the presence of vascular blush as a predictor of failure, with a failure of nonoperative management of 13% in that series. This finding led to an alteration in our management scheme, which now includes the aggressive identification and embolization of splenic artery pseudoaneurysms. METHODS: The medical records of 524 consecutive patients with blunt splenic injury managed over a 4.5-year period were reviewed for the following information: age, Injury Severity Score (ISS), American Association for the Surgery of Trauma splenic injury grade (SIG), method and outcome of management. RESULTS: Of the patients, 66% were male with a mean age of 32 +/- 16, and mean ISS of 25 +/- 13. A total of 180 patients (34%) were managed with urgent operation on admission (81% splenectomy (SIG 4.0), 19% splenorrhaphy (SIG 2.6)). The remaining 344 patients (66%) were hemodynamically stable and underwent computed tomographic scan and planned nonoperative management. Of these patients, 322 patients (94%) were successfully managed nonoperatively (61% of total splenic injuries). In 26 patients (8%), a contrast blush identified on computed tomographic scan was confirmed as a parenchymal pseudoaneurysm on arteriography. Twenty patients (SIG, 2.8) were successfully embolized. In six patients, technical failure precluded embolization; all required splenectomy (SIG, 4.0). A total of 22 patients (6%) failed nonoperative management, including the six with unsuccessful embolization attempts. Sixteen patients (SIG, 3.0) who had no evidence of pseudoaneurysm were explored for a falling hematocrit, hemodynamic instability, or a worsening follow-up computed tomography: 13 patients had splenectomy, and three patients had splenorrhaphy. CONCLUSIONS: Aggressive surveillance for and embolization of posttraumatic splenic artery pseudoaneurysms improved the rate of successful nonoperative management of blunt splenic trauma to 61%, with a nonoperative failure rate of only 6%. In comparison with our previous work, this reduction in failure of nonoperative management is a significant improvement (p < 0.03).

Adolescent↗

PubMed1998

Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients.

BACKGROUND: Perflubron is a perfluorocarbon with unique physical characteristics. It has twice the density of water, allows free diffusion of O2 and CO2, is easily dispersed, and is insoluble. Thus, it can act as "liquid positive end-expiratory pressure" to recruit collapsed alveoli and improve oxygenation. Results of laboratory studies suggest that perflubron exerts an anti-inflammatory effect on alveolar cells. Limited clinical data in neonates and adults with severe acute respiratory distress syndrome are promising. We present a single institution's experience with partial liquid ventilation (PLV) in trauma patients compared with conventional mechanical ventilation (CMV) with particular attention to the alveolar inflammatory response. METHODS: Ventilated patients with bilateral lung injury and PaO2/FIO2 < 300 were eligible in this prospective multicenter trial. Perflubron was administered by means of the endotracheal tube to fill up to functional residual capacity (approximately 30 mL/kg), followed by supplemental doses up to 96 hours. At this institution, bronchoscopy with bronchoalveolar lavage was performed serially for white blood cell count, protein, interleukin (IL)-1, IL-6, IL-8, and IL-10, and analyzed as early (< 48 hours) and late (48-96 hours). Clinical response was defined as a sustained 10% increase in PaO2/FIO2 at 48 hours. RESULTS: 16 patients were enrolled: 12 PLV patients and 4 CMV patients. There were no differences between groups relative to sex, Injury Severity Score, or initial PaO2/FIO2. There were no major outcome differences between groups in this pilot study relative to pneumonia (50% PLV and 75% CMV), deaths (one death in each group caused by multiple organ failure), or for oxygenation after 5 days. Eight PLV patients were responders (PLV-R) compared with four patients who did not (PLV-NR). The main differences between these subgroups was time from injury to study (1.8 days for PLV-R vs. 5.8 for PLV-NR, p < 0.02) and age (30 years for PLV-R vs. 42 years for PLV-NR, p < 0.04). Both white blood cell count and protein were higher in CMV, suggesting a greater inflammatory response. Neutrophils were significantly higher in CMV, despite equal IL-8 levels in both PLV and CMV. The inflammatory cytokines IL-1 and IL-6 were greater in CMV, and the anti-inflammatory IL-10 was lower in PLV. CONCLUSION: Early institution of partial liquid ventilation is effective at reducing the alveolar inflammatory response. Perflubron exhibits an anti-inflammatory effect in the alveolar environment with reduction of proinflammatory IL-1 and IL-6 (possibly removing a stimulus for IL-10), white blood cell count, and protein capillary leak. PLV also reduces alveolar neutrophils independent of IL-8. Further characterization of this altered inflammatory response is necessary.

Adolescent↗

PubMed1998

Cardiopulmonary function after pulmonary contusion and partial liquid ventilation.

PURPOSE: To compare the effects of mechanical ventilation with either positive end-expiratory pressure (PEEP) or partial liquid ventilation (PLV) on cardiopulmonary function after severe pulmonary contusion. METHODS: Mongrel pigs (32 +/- 1 kg) were anesthetized, paralyzed, and mechanically ventilated (8-10 mL/kg tidal volume; 12 breaths/min; FiO2 = 0.5). Systemic hemodynamics and pulmonary function were measured for 7 hours after a captive bolt gun delivered a blunt injury to the right chest. After 5 hours, FiO2 was increased to 1.0 and either PEEP (n = 7) in titrated increments to 25 cm H2O or PLV with perflubron (LiquiVent, 30 mL/kg, endotracheal) and no PEEP (n = 7) was administered for 2 hours. Two control groups received injury without treatment (n = 6) or no injury with PLV (n = 3). Fluids were liberalized with PEEP versus PLV (27 +/- 3 vs. 18 +/- 2 mL.kg-1.h-1) to maintain cardiac filling pressures. RESULTS: Before treatment at 5 hours after injury, physiologic dead space fraction (30 +/- 4%), pulmonary vascular resistance (224 +/- 20% of baseline), and airway resistance (437 +/- 110% of baseline) were all increased (p < 0.05). In addition, PaO2/FiO2 had decreased to 112 +/- 18 mm Hg, compliance was depressed to 11 +/- 1 mL/cm H2O (36 +/- 3% of baseline), and shunt fraction was increased to 22 +/- 4% (all p < 0.05). Blood pressure and cardiac index remained stable relative to baseline, but stroke index and systemic oxygen delivery were depressed by 15 to 30% (both p < 0.05). After 2 hours of treatment with PEEP versus PLV, PO2/FiO2 was higher (427 +/- 20 vs. 263 +/- 37) and dead space ventilation was lower (4 +/- 3 vs. 28 +/- 7%) (both p < 0.05), whereas compliance tended to be higher (26 +/- 2 vs. 20 +/- 2) and shunt fraction tended to be lower (0 +/- 0 vs. 7 +/- 4). With PEEP versus PLV, however, cardiac index, stroke index, and systemic oxygen delivery were 30 to 60% lower (all p < 0.05). Furthermore, although contused lungs showed similar damage with either treatment, the secondary injury in the contralateral lung (as manifested by intra-alveolar hemorrhage) was more severe with PEEP than with PLV. CONCLUSIONS: Both PEEP and PLV improved pulmonary function after severe unilateral pulmonary contusion, but negative hemodynamic and histologic changes were associated with PEEP and not with PLV. These data suggest that PLV is a promising novel ventilatory strategy for unilateral pulmonary contusion that might ameliorate secondary injury in the contralateral uninjured lung.

Animals↗

PubMed1998

Impact of stomach and colon injuries on intra-abdominal abscess and the synergistic effect of hemorrhage and associated injury.

BACKGROUND: Colon wounds are recognized to be highly associated with intra-abdominal abscess (IAA) after penetrating trauma, whereas gastric wounds are thought to contribute minimally to abscess because of the bactericidal effect of low pH. This study evaluated the impact of stomach or colon wounds, the contribution of other risk factors, and associated abdominal injuries on IAA. METHODS: Patients with penetrating colon or stomach wounds during a 10-year period were reviewed and stratified by age, Injury Severity Score, transfusions, and associated abdominal injuries. Early deaths (<48 hours) from hemorrhage were excluded. Outcomes analyzed were IAA and death. RESULTS: A total of 812 patients were identified. There were 32 late deaths (4%), of which 28% were attributable to IAA and multiple organ failure. IAA rates for isolated stomach or colon wounds were 0 and 4.2%, respectively. The presence of associated injuries increased IAA rates to 7.5 and 8.8%, respectively. Independent predictors of IAA determined by multivariate analysis included age, transfusions, gunshot wounds, and associated injuries to the liver, pancreas, and kidney. CONCLUSION: Gastric injuries are equivalent to colon wounds in their contribution to IAA. Contamination from either organ without associated injury is minimally associated with IAA, but injury to both appears synergistic. The immunosuppressive effects of age and hemorrhage, in addition to significant associated injury, enhance the development of IAA.

Abdominal Abscess↗

PubMed1998

Determinants of myocardial performance after blunt chest trauma.

OBJECTIVE: This study investigates whether factors that determine myocardial performance (preload, afterload, heart rate, and contractility) are altered after isolated unilateral pulmonary contusion. METHODS: Catheters were placed in the carotid arteries, left ventricles, and pulmonary arteries of anesthetized, ventilated (FiO2=0.5) pigs (31.2+/-0.6 kg; n=26). A unilateral, blunt injury to the right chest was delivered with a captive bolt gun (n=17) followed by tube thoracostomy. To control for anesthesia and instrumentation at FiO2 of 0.5, one group received tube thoracostomy only (sham injury; n=6). To control for effects of hypoxia without chest injury, an additional sham-injury group (n=3) was ventilated with FiO2 of 0.12. To generate cardiac function (i.e., Starling) curves, lactated Ringer's solution was administered in three bolus infusions at serial time points; the slope of stroke index versus ventricular filling pressure defines cardiac contractility. RESULTS: By 4 hours after pulmonary contusion, pulmonary vascular resistance, airway resistance, and dead space ventilation were increased, whereas PaO2 (72+/-6 mm Hg at FiO2=0.5) and dynamic compliance were decreased (all p < 0.05). Despite profound lung injury, arterial blood pressure, heart rate, cardiac filling pressures, and output remained within the normal range, which is inconsistent with direct myocardial contusion. The slope of pulmonary capillary wedge pressure versus left ventricular end-diastolic pressure (LVEDP) regression was reduced by more than 50% from baseline (p < 0.05), but there was no significant change in the slope of the central venous pressure versus LVEDP regression. By 4 hours after contusion, the slope of the stroke index versus LVEDP curve was reduced by more than 80% from baseline (p < 0.05). By the same time after sham injury with FiO2 of 0.12 (PaO2 < 50 mm Hg), the regression had decayed a similar amount, but there was no change in the slope after sham injury with FiO2 of 0.5 (PaO2 > 200 mm Hg). CONCLUSION: After right-side pulmonary contusion, the most often used estimate of cardiac preload (pulmonary capillary wedge pressure) does not accurately estimate LVEDP, probably because of changes in the pulmonary circulation or mechanics. Central venous pressure is a better estimate of filling pressure, at least in these conditions, probably because it is not directly influenced by the pulmonary dysfunction. Also, ventricular performance can be impaired by depressed myocardial contractility and increased right ventricular afterload even with normal left ventricular afterload and preload. It is thus conceivable that occult myocardial dysfunction after pulmonary contusion could have a role in the progression to cardiorespiratory failure even without direct cardiac contusion.

Animals↗

PubMed1998

Transient inhibition of CD18-dependent leukocyte functions after hemorrhage and polymicrobial sepsis.

BACKGROUND: The goals were (1) to characterize physiologic changes after a combined insult of hemorrhage plus sepsis in a large animal model and (2) to determine whether transient inhibition of the neutrophil CD18 adherence receptor during fluid resuscitation impairs host defense during recovery from this injury. METHODS: Two series of experiments were performed in anesthetized swine. In the first series (n = 22), the cecum was ligated and incised immediately before 35% hemorrhage. After 1 hour, shed blood plus supplemental fluid was administered to restore and stabilize hemodynamics. On the basis of these results, a second series examined effects of anti-CD18 (2 mg/kg R15.7; n = 9) or its saline placebo (n = 10) administered during fluid resuscitation. RESULTS: In the first series the mortality rate was 41% (9 of 22). Early deaths occurred 3.0 +/- 0.8 days after injury and were distinguished by significantly lower neutrophil counts on resuscitation. Those alive a 7 days had intraabdominal abscesses and bacteremia. Alveoli and peribronchial spaces were congested, with edema and fibrin deposition in capillaries and alveoli. Livers were congested with biliary stasis. Despite these pathologic findings, hemodynamic, electrolyte, and serum enzyme changes were minimal. In the second series the mortality rate at 4 days was 30% with placebo (3 of 10) versus 33% with anti-CD18 (3 of 9). Lung changes (i.e., pneumonia, pleuritis, thrombosis, and edema) were similar in both groups, but liver congestion and hemorrhage were attenuated by anti-CD18. Some aspects of host defense were altered by anti-CD18. At 24 and 48 hours the oxidative burst potential for circulating granulocytes was 208% +/- 57% and 383% +/- 73% with placebo versus 1273% +/- 351% and 762% +/- 226% in anti-CD18. At 72 hours the granularity of circulating neutrophils was unchanged from baseline with placebo but was reduced to 82% +/- 5% by anti-CD18. At 48 hours lipopolysaccharide-evoked tumor necrosis factor production in vitro was reduced to 62% +/- 22% with placebo but was increased to 148% +/- 16% with anti-CD18. CONCLUSIONS: Anti-CD18 during fluid resuscitation did not increase vulnerability to endogenous pathogens because the transient inhibition of neutrophil demargination was balanced by enhanced oxidative burst, degranulation, and production of tumor necrosis factor in circulating cells later during recovery. Thus a single administration of antiadhesion therapy does not worsen posttrauma outcome even if given during ongoing sepsis.

Animals↗

PubMed1998

Iliac artery ischemic: analysis of risks for ischemic complications.

Risk factors for lower extremity ischemic complications (ICs) following iliac arterial injuries have not been addressed. Patients with penetrating iliac artery injuries over a 15-year period were reviewed. IC was defined as compartment syndrome with or without tissue loss. Patients with iliac artery repair who developed ICs were compared with those without ICs (excluding early deaths from hemorrhagic shock). Comparison included demographics, severity of shock, physical examination, and operative findings. There were 94 arterial injuries in 80 patients (34 common iliac, 23 internal iliac, and 37 external iliac). There were 26 deaths (33%), and 3 patients were excluded for technical reasons. Of the 51 who underwent arterial reconstruction, 34 had no ischemia, whereas 17 (33%) had ICs (9 with tissue loss and 8 with compartment syndrome only). Immediate fasciotomies were performed in 6 of the IC patients due to the early recognition of compartment syndrome; 1 required amputation from the profound ischemia. Delayed recognition of compartment syndrome in the remaining 11 IC patients resulted in eight amputations (P < 0.05). We conclude that ICs following iliac arterial injuries significantly correlate with shock as indicated by systemic pH, lactate and transfusion requirements, and a preoperative pulseless extremity. In these patients, close monitoring of compartment pressures is necessary, and immediate fasciotomies should be strongly considered.

Adult↗