Comparing complications of small-bore chest tubes to large-bore chest tubes in the setting of delayed hemothorax: a retrospective multicenter cohort study.

BACKGROUND: Previous studies have provided initial data suggesting that small-bore (SB, ≤ 14Fr) chest tubes have the same efficacy as large-bore (LB, > 14 Fr) chest tubes for acute hemothorax (HTX), but data continue to be lacking in the setting of delayed HTX. This study compared complications of SB chest tubes to LB tubes in patients with delayed HTX. METHODS: This was a retrospective observational study across 7.5 yrs. at 6 Level 1 trauma centers. Patients were included if 1) diagnosed with a HTX or > 1 rib fracture with bloody effusion from chest tube; 2) initial chest tube placed ≥36 h of hospital admission. Patients were excluded for hemopneumothoraces. The primary endpoint was having at least one of the following chest tube complications: tube replacement, VATS, tube falling out, tube clogging, pneumonia, retained HTX, pleural empyema. Secondary outcomes included chest tube output volume and drainage rate. Dependent/independent and parametric/non-parametric analyses were used to assess primary and secondary outcomes. RESULTS: There were 160 SB patients (191 tubes) and 60 LB patients (72 tubes). Both comparison groups were similar in multiple demographic, injury, clinical features. The median (IQR) tube size for each group was as follows: SB [12 Fr (12-14)] and LB [32 Fr (28-32)]. The risk of having at least one chest tube complication was similar for LB and SB chest tubes (14% vs. 18%, p = 0.42). LB tubes had significantly larger risk of VATS, while SB tubes had significantly higher risk of pneumonia. SB tubes had significantly slower least squares (LS) mean initial output drainage rate compared to LB tubes (52.2 vs. 213.4 mL/hour, p < 0.001), but a non-parametric analysis suggested no significant difference in median drainage rates between groups 39.7 [23.5-242.0] mL/hr. vs. 38.6 [27.5-53.8], p = 0.81. LB and SB groups had similar initial output volume (738.0 mL vs. 810.9, p = 0.59). CONCLUSIONS: There was no clearly superior chest tube diameter size; both chest tube sizes demonstrated risks and benefits. Clinicians must be aware of these potential tradeoffs when deciding on the diameter of chest tube for the treatment of delayed HTXs.

The effect of orthopaedic surgeons' and interventional radiologists' availability on the priority treatment sequence for hemodynamically unstable pelvic fractures: a survey of US Level I trauma centers.

BACKGROUND: Most guidelines recommend both pelvic packing (PP) and angioembolization for hemodynamically unstable pelvic fractures, however their sequence varies. Some argue to use PP first because orthopaedic surgeons are more available than interventional radiologists; however, there is no data confirming this. METHODS: This cross-sectional survey of 158 trauma medical directors at US Level I trauma centers collected the availability of orthopaedic surgeons and interventional radiologists, the number of orthopaedic trauma surgeons trained to manage pelvic fractures, and priority treatment sequence for hemodynamically unstable pelvic fractures. The study objective was to compare the availability of orthopaedic surgeons to interventional radiologists and describe how the availability of orthopaedic surgeons and interventional radiologists affects the treatment sequence for hemodynamically unstable pelvic fractures. Fisher's exact, chi-squared, and Kruskal-Wallis tests were used, alpha = 0.05. RESULTS: The response rate was 25% (40/158). Orthopaedic surgeons (86%) were on-site more often than interventional radiologists (54%), p = 0.003. Orthopaedic surgeons were faster to arrive 39% of the time, and interventional radiologists were faster to arrive 6% of the time. There was a higher proportion of participants who prioritized PP before angioembolization at centers with above the average number (> 3) of orthopaedic trauma surgeons trained to manage pelvic fractures, as among centers with equal to or below average, p = 0.02. Arrival times for orthopaedic surgeons did not significantly predict prioritization of angioembolization or PP. CONCLUSIONS: Our results provide evidence that orthopaedic surgeons typically are more available than interventional radiologists but contrary to anecdotal evidence most participants used angioembolization first. Familiarity with the availability of orthopaedic surgeons and interventional radiologists may contribute to individual trauma center's treatment sequence.

Multimodal imaging does not delay intravenous thrombolytic therapy in acute stroke.

BACKGROUND AND PURPOSE: Patients with acute ischemic stroke require immediate medical treatment, and a CT to rule out hemorrhage is required before tPA. We adapted our protocol to include multimodal CT: unenhanced CT, CTA, and PCT. The purpose of this study was to determine whether multimodal CT imaging delays initiation of IV tPA beyond 60 minutes from hospital arrival. MATERIALS AND METHODS: All patients admitted during 3 years through the ED with a stroke alert and time from symptom onset to hospital arrival <2.5 hours were included. We examined 2 subgroups (multimodal CT versus unenhanced CT) to determine whether multimodal CT delayed tPA administration. Logistic regression was used to identify variables that predicted tPA within 60 minutes. RESULTS: There were 123 patients in the analysis, including 108 patients who were examined with multimodal CT. The median time from arrival to tPA was 56 minutes and was shorter for patients examined with multimodal CT (55 versus 78 minutes, P = .02). After adjustment, variables that were associated with tPA administration within 60 minutes included prehospital stroke alert (OR = 3.47, P = .03), time to CT (OR = 0.94, P = .01), and onset-to-arrival time (OR = 1.02, P = .04). There was no statistically significant difference in the odds of receiving timely tPA for multimodal versus unenhanced CT (OR = 3.99, P = .07). CONCLUSIONS: In our single-center experience, the use of multimodal imaging in patients with acute stroke did not delay IV tPA beyond 60 minutes. Further study is needed to assess the feasibility of the routine use of multimodal imaging in the acute stroke setting.

Attenuation of trace element-mediated injury during ischemia and reperfusion by an N-terminus analogue of human albumin (H4DUS60131).

The N-terminus region of human albumin binds strongly to trace metals (Co, Cu, Ni). Ischemia, acidosis and reperfusion can cause a marked increase in plasma free Cu and its normal regulation by plasma proteins may be overwhelmed and predispose to oxidative injury by Cu-catalyzed oxyradical production. H4DUS60131 is an analogue of the N-terminus of human albumin, it binds copper tightly and in vitro, is a potent inhibitor of Cu-catalyzed radical formation. We have tested the ability of H4DUS60131 to reduce injury during ischemia and reperfusion in isolated blood-perfused rat hearts (n = 6/group) subjected to 20-min aerobic perfusion, followed by a 2-min infusion of saline or saline plus H4DUS60131. Following infusion, hearts were subjected to 30-min global ischemia plus 40-min reperfusion. The 2-min infusion was repeated in both groups at the start of reperfusion. In the vehicle controls, left ventricular developed pressure recovered to only 15.3 +/- 3.2%, whereas the H4DUS60131 group recovered to 50.5 +/- 9.3% (p < 0.005). The H4DUS60131 group normalised their left ventricular end diastolic pressure more quickly and completely than the controls (44.1 +/- 11.5 vs. 91.5 +/- 5.5 mm Hg). In conclusion, H4DUS60131 greatly improves the recovery of the rat heart from ischemia and reperfusion and may represent a novel approach to the limitation of myocardial injury.

An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species.

Copper mobilization and redox activity form damaging reactive oxygen species (ROS) and are implicated in the pathogenesis of ischemia-reperfusion injury, chronic inflammation, Alzheimer's disease, aging, and cancer. Protein sequestration of Cu(II) ions has been shown to prevent ROS-generating reactions. The first four amino acids of the N-terminus of human albumin, Asp-Ala-His-Lys (DAHK), form a tight binding site for Cu(II) ions. We synthesized several analogs, including the enantiomer d-DAHK, to study their effects on copper-induced hydroxyl radical and superoxide formation in the presence of ascorbate. d-DAHK prevented thiobarbituric acid-reactive species (TBARS) formation within physiological and acidic pH ranges (7.5-6.5) and inhibited low-density lipoprotein lipid peroxidation. A d-DAHK/Cu complex exhibited superoxide dismutase-like activity by significantly inhibiting superoxide formation. These in vitro results suggest that d-DAHK may shift the Cu(II)-binding equilibrium from the exchangeable Cu(II) pool to the tightly-bound, nonexchangeable pool, prevent ROS formation, and potentially provide therapeutic benefit for ROS-related diseases.

Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I.

BACKGROUND: Previous reports suggest that ischemic conditions rapidly reduce the capacity of human albumin to bind exogenous cobalt. A new assay based on human albumin-cobalt binding (ACB) may help detect early myocardial ischemia. We investigated altered ACB during the first 24 hours after transient ischemia induced during elective percutaneous transluminal coronary angioplasty (PTCA). We then compared ACB assay results with creatine kinase isoenzyme (CK-MB), myoglobin, and cardiac troponin I (cTn-I) values after PTCA. METHODS AND RESULTS: In 41 patients undergoing elective PTCA, plasma samples were tested for the ACB assay, CK-MB, myoglobin, and cTn-I before, immediately after, and 6 and 24 hours after PTCA. Thirteen additional patients served as a control group with albumin-cobalt assays performed before and after diagnostic coronary catheterization without angioplasty. ACB assay results demonstrated a significant mean percent difference (10.1%) immediately after PTCA compared with baseline (P < .000001) and returned to baseline by 6 hours after PTCA. ACB assay differences immediately after PTCA were significantly greater than in the control group (10.1% vs -0.9%, P < .001). Mean CK-MB, myoglobin, and cTn-I values were not elevated above baseline immediately after PTCA but were significantly elevated above baseline 6 and 24 hours after PTCA. CONCLUSIONS: These preliminary results suggest that human albumin undergoes a significant reduction in its capacity to bind exogenous cobalt soon after transient coronary occlusion during human PTCA and before significant elevations of CK-MB, myoglobin, or cTn-I. Further confirmatory investigations are warranted to determine if the ACB assay is a useful diagnostic test for early myocardial ischemia.

Asp-Ala-His-Lys (DAHK) inhibits copper-induced oxidative DNA double strand breaks and telomere shortening.

Both DNA and the telomeric sequence are susceptible to copper-mediated reactive oxygen species (ROS) damage, particularly damage attributed to hydroxyl radicals. In this study, ROS-induced DNA double strand breaks and telomere shortening were produced by exposure to copper and ascorbic acid. Asp-Ala-His-Lys (DAHK), a specific copper chelating tetrapeptide d-analog of the N-terminus of human albumin, attenuated DNA strand breaks in a dose dependent manner. d-DAHK, at a ratio of 4:1 (d-DAHKCu), provided complete protection of isolated DNA from double strand breaks and, at a ratio of 2:1 (d-DAHKCu), completely protected DNA in Raji cells exposed to copper/ascorbate. Southern blots of DNA treated with copper/ascorbate showed severe depletion and shortening of telomeres and Raji cell treated samples showed some conservation of telomere sequences. d-DAHK provided complete telomere length protection at a ratio of 2:1 (d-DAHKCu). The human albumin N-terminus analog, d-DAHK, protects DNA and telomeres against copper-mediated ROS damage and may be a useful therapeutic adjunct in ROS disease processes.

Characterization of the Co(2+) and Ni(2+) binding amino-acid residues of the N-terminus of human albumin. An insight into the mechanism of a new assay for myocardial ischemia.

Patients suffering from myocardial ischemia reportedly exhibit reduced in vitro binding of exogenous Co(2+) to the N-terminal of human serum albumin (HSA). The purpose of our investigation was to simulate changes in the N-terminus of HSA that may account for these ischemia-induced modifications to the cobalt binding site. HPLC, LC-MS and (1)H NMR analyses have shown that the N-terminal region of HSA Asp-Ala-His-Lys binds the transition metals Co(2+) and Ni(2+). Synthetic peptides with the first 2-12 amino acids of the HSA sequence demonstrated that the first three amino acids, Asp-Ala-His, are essential for strong binding of cobalt. Modification of the N-terminus peptide of HSA by way of N-acetylation or the deletion of one or more amino acid resulted in no binding of cobalt. Because the degradation of the susceptible, specific transition metal binding site of HSA may account for the decreased cobalt binding observed during ischemic events, an assay that detects this reduced binding could be useful in the diagnosis of ischemia.

A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia-a preliminary report.

We initially observed a phenomenon of reduced in vitro binding of exogenous cobalt [Co(II)] to the N-terminus of human serum albumin (HSA) in emergency chest pain patients with early onset unstable angina and myocardial infarction. We then developed a colorimetric assay to measure cobalt-HSA binding and record the results in absorbance units (ABSU). In a preliminary clinical study of 139 emergency patients with acute chest pain, 99 patients with evidence of myocardial ischemia (Group 1) had elevated assay levels (mean ABSU +/- SD; 0.519 +/- 0.086) compared to 40 patients (Group 2) with no evidence of ischemia (0.316 +/- 0.092) (p < 0.00001). In Group 1, 95 of 99 (96.0%) patients had levels higher than a decision threshold of 0.400 ABSU and in Group 2, 37 of 40 (92.5%) samples had higher cobalt binding capacity (ABSU

Transient monocyte release of interleukin-10 in response to traumatic brain injury.

A significant component of the immune response to trauma results in the systemic presence of cytokines which have the potential to suppress the patient's immune response to infection and contribute to post-injury complications. We assayed peripheral blood leukocytes obtained from 10 patients with head trauma to determine their production of interleukin (IL). Serum was assayed for the presence of IL-10, TGFbeta1, and IFNgamma by ELISA. Peripheral blood leukocytes were screened for intracellular IL-10 and IFNgamma by fluorescence-activated flow cytometry, and cytokine-specific mRNA was detected by the polymerase chain reaction. We detected an immediate, but transient, presence of IL-10 in the sera of all 10 patients who suffered head trauma. IL-10-specific intracytoplasmic immunofluorescence was also detected immediately after injury in peripheral blood monocytes, but not in lymphocytes or granulocytes. IL-10-specific mRNA was detected in peripheral blood leukocytes in only 50% of patients immediately after injury, when the highest serum levels of IL-10 were observed. Our data indicates that release of pre-formed IL-10 by monocytes contributes to the presence of IL-10 found in patient peripheral blood immediately after head injury.

Protracted metabolic acidosis: the impact of acute ethanol in hemorrhagic shock.

The effects of acute ethanol administration on acid-base balance and hemodynamic parameters were studied in a canine model. Ten mongrel dogs, anesthetized and maintained on a volume ventilator, underwent splenic artery ligation 30 minutes prior to study. Group A (N = 5) served as controls. Thirty minutes after drug administration, the animals underwent a 20-cc/kg hemorrhage over 15 minutes. Thirty minutes postphlebotomy, resuscitation was performed with the same volume of homologous blood. Acid-base and hemodynamic parameters were monitored over 3.5 hours. Ethanol levels peaked 60 minutes following administration at 207 +/- 13 mg%. During the entire study, no differences were observed in heart rate, pulmonary capillary wedge pressure, systemic vascular resistance index, pO2, or pCO2, between the two groups. Following hemorrhage, statistically significant decreases in pH, mean arterial pressure (MAP), cardiac index (CI), and left ventricular stroke work index (LVSWI) developed in group A compared to controls. Maximal disparity developed in pH (7.21 +/- 0.05 to 7.33 +/- 0.02, P < 0.01), MAP (67 +/- 11 v 110 +/- 9 torr, P < 0.01), CI (1.69 +/- 0.24 compared to 2.72 +/- 0.19 L/min/M2, and LVSWI (18.7 +/- 1.2 compared to 44.9 +/- 4.8 gr-meter/M2/beat, P < 0.01) at 60, 45, 30, and 75 minutes postphlebotomy. In this study, ethanol directly or indirectly caused an increased metabolic acidosis and myocardial depression in the post-hemorrhage period.

The benefits of 7.5% NaCl/6% dextran 70 (HSD) for prehospital resuscitation of hemorrhagic shock: improved oxygen transport.

The purpose of this study was to compare the benefit of small volume hypertonic saline/dextran (HSD) versus the risk of obligatory time to administer it on-scene in a model of acute hemorrhagic shock. Dogs were bled to a mean arterial pressure (MAP) of 20 mmHg and then randomized to either: a) direct transport to the emergency department (ED) or b) 10 min delay to insert an iv HSD (4 ml/kg) infusion over 5 min, and then transport. The animals receiving HSD had improved (P less than 0.05) cardiac work and oxygen consumption during transport (MAP = 59 +/- 3 vs 38 +/- 4 mmHg; cardiac index (CI) = 3.2 +/- 0.2 vs 1.3 +/- 0.1 L min-1 M-2; O2CI = 115 +/- 7 vs 104 +/- 7 ml min-1 M-2), paralleled by reduced serum lactate (5.3 +/- 0.8 vs 7.0 +/- 2.3 mmol/L) and decreased metabolic acidosis. The benefits of HSD in attenuating shock-induced oxygen debt were corroborated by lower O2CI (98 +/- 4 vs 112 +/- 5 ml min-1 M-2) and higher pH (7.30 +/- 0.01 vs 7.24 +/- 0.02) in the postresuscitation period.

The benefits of 7.5 NaCl/6 dextran 70 (HSD) for prehospital resuscitation of hemorrhagic shock: improved oxygen transport

The purpose of this study was to compare the benefit of small volume hyperonic saline/dextran (HSD) versus the risk of obligatory time to administer it on-scene in a model of acute hemorrhagic shock. Dogs were bled to a mean arteiral pressure (MAP) of 20 mmHg and the randomized to either: a) direct transport to the emergency department (ED) or b) 10 min delay to insert an iv HSD (4 ml/Kg) infusion over 5 min, and then transport. The animals receiving HSD had improved (P<0.05) cardiac work and oxigen consumption during transport (MAP = 59 ñ 3 vs 38 ñ 4 mmHg; cardiac index (CI) = 3.2 ñ 0.2 vs 1.3 ñ 0.1 L min-1 M-2; O2CI = 115 ñ 7 vs 104 ñ 7 mlmin-1M-2), paralleled by reduced serum lactate (5.3 ñ 0.8 vs 7.0 ñ 2.3 mmol/L) and decreased metabolic acidosis. The benefitsof HSD in attenuating shock-induced oxygen debt were corroborated by lower O2CI(98 ñ 4 vs 112 ñ 5 ml min-1 M-2) and higher pH (7.30 ñ 0.01 vs 7.24 ñ 0.02) in the postresuscitation period

Urinary lactic dehydrogenase as a marker of renal injury in blunt trauma patients with hematuria.

We evaluated the use of urinary lactic dehydrogenase (LDH) in predicting renal injury in a convenience sample of 36 blunt trauma patients with hematuria. The mean +/- SEM urinary LDH for the five patients with renal injuries was 129.4 +/- 35 U/L, which was not significantly different from the mean urinary LDH levels in either the 22 patients without demonstrable genitourinary or retroperitoneal injuries (92.9 +/- 20.7 U/L) or the nine patients with nonrenal genitourinary or retroperitoneal injuries (165 +/- 46 U/L). Urinary LDH at a threshold of 135 U/L was more specific (75% vs 53%, P less than .01) and more accurate (74% vs 57%, P less than .01) than hematuria at a threshold of 50 red blood cells per high-power field in predicting lacerations of the kidney or ureter; urinary LDH was less sensitive than hematuria at these thresholds (67% vs 100%), but not significantly. We conclude that urinary LDH is a nonspecific marker of cellular disruption anywhere along the genitourinary tract in otherwise healthy blunt trauma patients.

Intravenous theophylline poisoning and multiple-dose charcoal in an animal model.

Large overdoses of IV theophylline (50 to 100 mg/kg) were administered to five canines on two separate occasions. On day one, with no charcoal administered, theophylline levels were serially obtained between ten minutes and 12 hours after infusion and the animals were recovered from anesthesia. Three days later the same dose of theophylline was administered, but then 50 g activated charcoal was placed through a nasogastric tube into the duodenum every hour for eight doses. In all five animals tested, activated charcoal significantly decreased the area under the serum concentration-time curve, decreased the half-life of elimination, and increased the clearance of theophylline. This effect on pharmacokinetics was not seen when the nasogastric tube was put into the stomach instead of the small bowel because the charcoal administered did not pass beyond the pylorus. In a separate experiment in which bile theophylline concentrations were measured, it was demonstrated that enhanced elimination was not from interruption of enterohepatic circulation of theophylline. This suggests that the demonstrated physiologic mechanism is that of gastrointestinal dialysis.

Management of acutely poisoned patients without gastric emptying.

During an 18-month period, 592 acute oral drug overdose patients were studied prospectively in a controlled, randomized fashion to determine the efficacy of gastric emptying procedures in altering clinical outcome. Patients presenting on even-numbered days had no gastric emptying procedures performed, and they were compared to patients presenting on odd-numbered days who received either syrup of ipecac or gastric lavage. Patients were carefully followed for evidence of subsequent clinical improvement or deterioration after initial management. Syrup of ipecac did not significantly alter the clinical outcome of patients who were awake and alert on presentation to the emergency department (ED). Gastric lavage in obtunded patients led to a more satisfactory clinical outcome (P less than .05) only if performed within one hour of ingestion. Gastric emptying procedures in the ED for initial treatment of drug overdose are generally not of benefit unless gastric lavage is performed within one hour of ingestion in obtunded patients.

Preparation of a new antivenin by affinity chromatography.

Polyacrylamide gel affinity chromatography was employed to isolate and purify antibodies to the antigens of the venoms of four rattlesnakes. The antivenins were studied for their neutralizing properties on a number of pharmacologic preparations. It was found that the purified antibodies (IgG) were more efficacious than the commercially prepared antivenin in neutralizing the lethal, cytolytic, hemorrhagic, platelet aggregating, and other deleterious effects of the venoms. In addition, the purified antibodies gave no evidence of producing anaphylaxis or anaphylactoid reactions in animals sensitized to horse serum. The proposed technique is also more simple than current production methods, is time-saving, and less expensive.

Utility of lavage alkaline phosphatase in detection of isolated small intestinal injury.

The ability of lavage alkaline phosphatase (LAP) to detect small intestinal injury was studied in 81 patients who underwent diagnostic peritoneal lavage following blunt and penetrating abdominal trauma. Patients with a grossly positive lavage were excluded. The LAP of five patients with small intestinal injury (79.0 +/- 41.7 IU/L) was significantly greater than in 76 cases without (1.2 +/- 0.4 IU/L; P less than .05). LAP greater than or equal to 3 was seen in six patients. Four had isolated small intestinal pathology, and one had combined small and large bowel injury. In three of these five, other lavage values were normal. One possible false positive occurred. The sensitivity of LAP greater than or equal to 3 (100%) exceeded that of usual lavage parameters in the detection of small intestinal injury. LAP may be a sensitive marker for small intestinal pathology in the immediate postinjury period.