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Biomedical subjects

M A Croce

Publications and source records attributed to M A Croce.

At least 19 recordsLinked to original sources

Intermittent and continuous ceftazidime infusion for critically ill trauma patients.

BACKGROUND: The adequacy of intermittent and continuous infusion ceftazidime for the treatment of nosocomial pneumonia in critically ill trauma patients was assessed by analyzing ceftazidime pharmacokinetics in relation to the minimum inhibitory concentration (MIC) and treatment outcome. METHODS: Serial blood samples were obtained during ceftazidime therapy in 31 trauma patients. Ceftazidime pharmacokinetics were compared with that of previously studied healthy volunteers. Ceftazidime pharmacokinetics were analyzed according to the time above the MIC and treatment outcome. RESULTS: Critically ill trauma patients had a significantly increased volume of distribution and clearance (0.32 +/- 0.14 L/kg and 2.35 +/- 0.89 mL. min(-1). kg(-1), respectively) compared with healthy volunteers (0.21 +/- 0.03 and 1.58 +/- 0.23 mL. min(-1). kg(-1)). The time above the MIC was >/=92% of the dosing interval for all patients and treatment outcomes were similar between the two treatment groups. CONCLUSIONS: Ceftazidime pharmacokinetics are significantly altered in critically ill trauma patients. Both intermittent and continuous ceftazidime regimens were equally effective for the treatment of nosocomial pneumonia caused by less virulent bacteria.

Adolescent↗

Blunt hepatic injury: a paradigm shift from operative to nonoperative management in the 1990s.

OBJECTIVE: To analyze the outcome of hemodynamically stable patients with blunt hepatic injury managed nonoperatively, and to examine the impact of this approach on the outcome of all patients with blunt hepatic injury. SUMMARY BACKGROUND DATA: Until recently, operative management has been the standard for liver injury. A prospective trial from the authors' institution had shown that nonoperative management could safely be applied to hemodynamically stable patients with blunt hepatic injury. The present study reviewed the authors' institutional experience with blunt hepatic trauma since that trial and compared the results with prior institutional experience. METHODS: Six hundred sixty-one patients with blunt hepatic trauma during the 5-year period ending December 1998 were reviewed (NONOP2). The outcomes were compared with two previous studies from this institution: operative 1985 to 1990 (OP) and nonoperative 1993 to 1994 (NONOP1). RESULTS: All 168 OP patients were managed operatively. Twenty-four (18%) of 136 NONOP1 patients and 101 (15%) of the 661 NONOP2 patients required immediate exploration for hemodynamic instability. Forty-two (7%) patients failed nonoperative management; 20 were liver-related. Liver-related failures of nonoperative management were associated with higher-grade injuries and with larger amounts of hemoperitoneum on computed tomography scanning. Twenty-four-hour transfusions, abdominal infections, and hospital length of stay were all significantly lower in the NONOP1 and NONOP2 groups versus the OP cohort. The liver-related death rate was constant at 4% in the three cohorts over the three time periods. CONCLUSIONS: Although urgent surgery continues to be the standard for hemodynamically compromised patients with blunt hepatic trauma, there has been a paradigm shift in the management of hemodynamically stable patients. Approximately 85% of all patients with blunt hepatic trauma are stable. In this group, nonoperative management significantly improves outcomes over operative management in terms of decreased abdominal infections, decreased transfusions, and decreased lengths of hospital stay.

Abdominal Abscess↗

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↗

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↗

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↗

Postoperative pneumonia.

Despite the advances made in surgical critical care, the diagnosis of one of the most common infections seen in critically ill patients remains a challenge. Ventilator-associated pneumonia is associated with a 20 to 25 per cent mortality rate. There are numerous risk factors for ventilator-associated pneumonia, including underlying disease, prolonged mechanical ventilation, direct lung injury, and shock. The standard clinical criteria for pneumonia are inaccurate. Quantitative cultures of bronchoalveolar lavage effluent are accurate for the diagnosis, and it is safe to base antibiotic therapy on the results of the quantitative cultures.

Cross Infection↗

Diagnosis of acute respiratory distress syndrome and differentiation from ventilator-associated pneumonia.

Acute respiratory distress syndrome (ARDS) remains a significant cause of morbidity and mortality in surgical intensive care unit patients. A relatively predictable sequence of pathophysiologic events occur in the lung, which involve inflammatory mediators and neutrophils. The characteristic radiographic findings of ARDS may mimic ventilator-associated pneumonia (VAP), making the diagnosis of VAP difficult. The standard clinical criteria of fever, leukocytosis, purulent sputum, and infiltrate on chest radiograph are not specific for pneumonia in the surgical patient. The use of bronchoscopy with bronchoalveolar lavage and quantitative cultures can differentiate local and systemic inflammatory response to injury or blood loss from invasive bacterial pneumonia. Basing antibiotic therapy solely on the results of quantitative cultures is safe, because quantitative cultures identify VAP in less than half the patients with clinical evidence of pneumonia. Empiric therapy should be based on the microbiology of the intensive care unit rather than the results of the Gram stain.

Anti-Bacterial Agents↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗