Computerized decision support for mechanical ventilation of trauma induced ARDS: results of a randomized clinical trial.

BACKGROUND: Variability and logistic complexity of mechanical ventilatory support of acute respiratory distress syndrome, and need to standardize care among all clinicians and patients, led University of Utah/LDS Hospital physicians, nurses, and engineers to develop a comprehensive computerized protocol. This bedside decision support system was the basis of a multicenter clinical trial (1993-1998) that showed ability to export a computerized protocol to other sites and improved efficacy with computer- versus physician-directed ventilatory support. The Memorial Hermann Hospital Shock Trauma intensive care unit (ICU) (Houston, TX; a Level I trauma center and teaching affiliate of The University of Texas Houston Medical School) served as one of the 10 trial sites and recruited two thirds of the trauma patients. Results from the trauma patient subgroup at this site are reported to answer three questions: Can a computerized protocol be successfully exported to a trauma ICU? Was ventilator management different between study groups? Was patient outcome affected? METHODS: Sixty-seven trauma patients were randomized at the Memorial Hermann Shock Trauma ICU site. "Protocol" assigned patients had ventilatory support directed by the bedside respiratory therapist using the computerized protocol. "Nonprotocol" patients were managed by physician orders. RESULTS: Of the 67 trauma patients randomized, 33 were protocol (age 40 +/- 3; Injury Severity Score [ISS] 26 +/- 3; 73% blunt) and 34 were nonprotocol (age 38 +/- 2; ISS 25 +/- 2; 76% blunt). For the protocol group, the computerized protocol was used 96% of the time of ventilatory support and 95% of computer-generated instructions were followed by the bedside respiratory therapist. Outcome measures (i.e., survival, ICU length of stay, morbidity, and barotrauma) were not significantly different between groups. Fio2 > or = 0.6 and Pplateau > or = 35 cm H2O exposures were less for the protocol group. CONCLUSION: A computerized protocol for bedside decision support was successfully exported to a trauma center, and effectively standardized mechanical ventilatory support of trauma-induced acute respiratory distress syndrome without adverse effect on patient outcome.

Nurses' retention of pain management knowledge.

Despite efforts to improve nurses' pain management knowledge, a lack of understanding about basic pain management concepts remains. This article presents results of a pilot study about the effectiveness of a pain management education program. Nurses' mean scores on pain management concepts tests increased from 56% to 76%. The scores are still low, and nurses need further education and reinforcement about basic pain management concepts.

Evaluation of clinician accuracy in describing gunshot wound injuries.

A large series of gunshot wounds is analyzed to determine, first, whether the wounds were described with enough detail to estimate the distance and direction of fire; and second, to utilize the autopsy description to determine accuracy. All of the University of Miami-Jackson Medical Center (UM-JMC) records coded as gunshot wounds and treated during calendar year 1995 were included in this study. The analysis is of 566 shootings from bullets in which 1259 wounds were described in the hospital records. Of the 1259 bullet wounds, the size and/or shape was described in only 63 (5%) and only four wounds (0.3%) had any indication of distance of fire. The location of the wound could be determined to within 3 cm in 655 (52%) and only 39 (3%) of the wounds were measured from some landmark. Directionality was neither indicated nor determinable in 897 (71%) of the wounds examined. Fifty-five (9%) cases resulted in death and were compared with medical examiner autopsies. Clinical information was inadequate for comparison in three (6%) of these cases. In 22 cases that were said to have one wound, only 14 (64%) of these were correctly documented. Of 16 cases with 2 wounds, 9 (56%) were correctly identified by the clinicians. When greater than 2 wounds were present (14), the clinicians were wrong 93% of the time. This study demonstrates that clinicians responsible for treating gunshot-wounded persons do not adequately document or interpret these wounds.

Role of cAMP in modulating relaxation kinetics and the force-frequency relation in mitral regurgitation heart failure.

The report is a discussion of previously published and newly analyzed results concerning the association between heart diseases and alterations in the force-frequency relation (FFR). The optimum stimulation frequency of the FFR is measured and compared in isolated left ventricular myocardium from non-failing hearts with atrial septal defect, coronary artery disease (without and with insulin dependent diabetes mellitus) and from failing hearts with mitral regurgitation, or idiopathic dilated cardiomyopathy. Specifically, we examine the role of altered control of the excitation-contraction coupling system in blunting the force-frequency relation. We use the percent slope of the FFR as a measure of changes in the frequency sensitivity of this control. Our finding of a linear, direct relation between optimum stimulation frequency and % slope across all disease types suggests both parameters are coupled to the same underlying mechanism. To investigate the possible role of altered control of the calcium pump in this mechanism, we analyzed the detailed relation between isometric twitch relaxation kinetics and stimulation frequency in mitral regurgitation myocardium (MR). In the presence of 0.5 microM forskolin the depressed slope and optimum frequency of the FFR and the prolonged half-time of twitch relaxation were all restored to values found in non-failing myocardium. We use the kinetics of isometric twitch relaxation as an index of changes in pumping rate that occur in response to changes in stimulation frequency or in intracellular cyclic adenosine monophosphate concentration. A mathematical model based on the Hill relations for calcium pump uptake rate and for isometric tension as a function of intracellular pCa is developed to simulate isometric twitch relaxation in MR and non-failing myocardium. The success of this model in simulating non-failing and failing twitch relaxation supports a proposed mechanism for the prolonged relaxation time and depressed FFR in MR involving depressed protein kinase-A activity (due to lowered cAMP or to a defect in the Ser16 site of phospholamban) as a mechanism of altered control of the calcium pump in MR heart disease.

Smooth, cardiac and skeletal muscle myosin force and motion generation assessed by cross-bridge mechanical interactions in vitro.

Differences in the mechanical properties of mammalian smooth, skeletal, and cardiac muscle have led to the proposal that the myosin isozymes expressed by these tissues may differ in their molecular mechanics. To test this hypothesis, mixtures of fast skeletal, V1 cardiac, V3 cardiac and smooth muscle (phosphorylated and unphosphorylated) myosin were studied in an in vitro motility assay in which fluorescently-labelled actin filaments are observed moving over a myosin coated surface. Pure populations of each myosin produced actin filament velocities proportional to their actin-activated ATPase rates. Mixtures of two myosin species produced actin filament velocities between those of the faster and slower myosin alone. However, the shapes of the myosin mixture curves depended upon the types of myosins present. Analysis of myosin mixtures data suggest that: (1) the two myosins in the mixture interact mechanically and (2) the same force-velocity relationship describes a myosin's ability to operate over both positive and negative forces. These data also allow us to rank order the myosins by their average force per cross-bridge and ability to resist motion (phosphorylated smooth > skeletal = V3 cardiac > V1 cardiac). The results of our study may reflect the mechanical consequence of multiple myosin isozyme expression in a single muscle cell.

Hibernation alters the frog's immune system.

The lymphomyeloid organs and blood leukocyte populations of the leopard frog, Rana pipiens, undergo conspicuous changes during hibernation at 4 degrees C. Within the blood, spleen, thymus, jugular bodies, and bone marrow there was a progressive loss of hemopoietic populations resulting in a marked lymphocyte depletion. Termination of the 135-day hibernation period resulted in the restoration of all hemopoietic elements in the blood and lymphomyeloid organs within 30 days. Frogs subjected to experimental hibernation and immunized showed weakened immune responses when brought from the hibernaculum. Plaque-forming cells (PFC) were lower in spleen, jugular bodies, and bone marrow, and serum antibody titers were also lower. Although the kinetics of the primary responses were essentially the same, the secondary responses differed suggesting major rearrangements with respect to the numbers of cells and their function in secreting antibody. The apparent lymphocyte aplasia may contribute to the absence of immunological responsiveness during periods of hibernation.

Fatal virus-associated hemophagocytic syndrome in a young adult producing nontraumatic splenic rupture.

A 24-year-old man with no previous medical history was admitted to a local hospital with pancytopenia after a recent "viral illness." During his hospitalization, he developed sudden abdominal distension and hypotension. Surgical exploration of his abdomen revealed a ruptured spleen. The spleen was removed, but the patient did not survive the operation. We investigated this unexpected and unexplained hospital death for any traumatic or iatrogenic injury. The cause of death after review of the clinical history, autopsy, and microscopic sections was virus-associated hemophagocytic syndrome (VAHS). VAHS consists of a generalized histiocytic proliferation and marked hemophagocytosis associated with a systemic viral infection. Clinically it presents as pancytopenia and organomegaly. This recently described entity is often confused with malignant histiocytosis. This is the first case report of VAHS producing nontraumatic splenic rupture, thus adding to the differential diagnosis of spontaneous splenic rupture and sudden natural death.

Sexual asphyxia in siblings.

We present an accidental autoerotic asphyxiation of a 24-year-old man. Further investigation revealed that 18 years earlier, his brother, then 13, had been found dead, hanging in the family bathroom. Although that death had been ruled a suicide, reevaluation of the death scene indicates that this was also an autoerotic asphyxiation. This is the first reported case of sexual asphyxia involving siblings.

Mesna excretion and ifosfamide nephrotoxicity in children.

To characterize the excretion of 2-mercaptoethanesulfonate sodium (mesna) administered by intermittent infusion, urinary concentrations of mesna and its corresponding inactive disulfide were measured during 50 courses of ifosfamide (1.6 g/m2 for 5 days) and mesna (400 mg/m2 at 0.25, 4, and 6 h after each ifosfamide dose) administered i.v. to 19 patients. Some patients had previously received nephrotoxic therapy that might influence the excretion of mesna and its associated uroprotective effects. The median urinary free thiol concentration increased to 3 mM by 1 h after mesna infusion, declining to background levels by 4 h. The rate of mesna excretion correlated with the creatinine clearance rate in a subset of six patients. The proportion of mesna recovered in urine within 4 h after infusion was lower (P less than 0.05) in children who had evidence of preexisting renal tubular damage. Ifosfamide-induced tubular proteinuria was associated with lower urinary mesna recovery. Low urinary mesna concentrations indicated potentially subtherapeutic renal tubular levels. However, ifosfamide nephrotoxicity was subclinical and is not necessarily linked to differences in mesna excretion.

Monitoring serum aminoglycoside concentrations in children with amphotericin B nephrotoxicity.

We prospectively studied the effect of amphotericin B therapy on aminoglycoside clearance in 20 consecutive children during the remission-induction phase of chemotherapy for acute myelocytic leukemia. Increases (greater than 50%) in the half-life for aminoglycoside excretion were not associated with antileukemic or aminoglycoside therapy alone but occurred in 12 of 17 children when amphotericin B was added to the antimicrobial regimen. Seven children had impaired aminoglycoside clearance without increases (greater than 50%) in serum creatinine; hence the resulting adjustments in aminoglycoside dosage would not have been made had we relied solely on serial measurements of serum creatinine. Evidence for increased excretion of the renal enzymes N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase during amphotericin B therapy suggested that damage to proximal tubular cells may contribute to the renal impairment that has been associated with this drug. Our findings underscore the value of monitoring serum aminoglycoside concentrations in children being treated with amphotericin B.

Massive metoprolol ingestion associated with a fatality--a case report.

An unusual fatality involving a 26-year-old male who intentionally ingested approximately 10 g of metoprolol is presented. Autopsy findings revealed foreign material in the gastric content with an acute thrombosis of the left anterior descending coronary artery. Microscopic studies showed evidence of an extremely early infarct. Metoprolol concentrations in the blood, liver, gastric content, and urine are reported by both capillary gas chromatography and ultraviolet spectrophotometric analysis. A review of the literature confirmed that little information has been published concerning intoxication with this drug.

Urinary N-acetyl-beta-D-glucosaminidase and serum creatinine concentrations predict impaired excretion of methotrexate.

We determined the risk of impaired excretion of methotrexate (MTX) in children with osteosarcoma, who also were receiving cisplatin, by analyzing urinary markers of renal tubular damage, as well as serum creatinine measured before each dose of MTX. MTX clearance was impaired in seven of the ten patients studied after cisplatin therapy. Patients with a urinary N-acetyl-beta-D-glucosaminidase (NAG) concentration of greater than 1.5 U/mmol creatinine or a greater than 50% increase in serum creatinine relative to the pretherapy level were approximately 30 times more likely to have MTX half-lives greater than 3.5 hours than were patients with lower values for these markers; MTX clearance was always impaired if both markers were elevated. If neither urinary NAG nor serum creatinine concentrations increased, the risk of impaired MTX excretion was negligible. Our findings demonstrate that urinary NAG and serum creatinine levels, measured before MTX administration, can be used to identify patients who will have difficulty in clearing the drug.

Potentiation of ifosfamide neurotoxicity, hematotoxicity, and tubular nephrotoxicity by prior cis-diamminedichloroplatinum(II) therapy.

We investigated the relationship between prior therapy and three distinct forms of toxicity that developed during ifosfamide administration (1.6 g/m2/day for 5 days) in 36 children with malignant solid tumors. Of ten therapies that were studied by multiple regression techniques, only the number of doses of cisplatin that patients had received was significantly related to neurotoxicity, hematotoxicity, and tubular nephrotoxicity, with the more severe cases occurring after three or more doses (P less than 0.05). Increased urinary concentrations of the renal tubular enzyme N-acetyl-beta-D-glucosaminidase, measured before each course of ifosfamide, were predictive of neurotoxicity (P = 0.02) and hematotoxicity (P = 0.01). We suggest that cisplatin-induced renal tubular damage, leading to the impaired clearance of ifosfamide metabolites, may account for this added toxicity.

Racial variation in the sternal extremity of the rib and its effect on age determination.

Most research on the aging process in the skeleton has not considered or elaborated differences that may exist between the races. Thus, techniques developed for the estimation of age assume that the racial background of the standards is compatible with the specimens to be assessed. However, racial differences in areas such as skeletal growth and bone density have been reported, along with specific variations in the aging process, in the ribs of disparate populations. The present investigation examines metamorphosis in the sternal ribs of American blacks (N = 53 males, N = 20 females), and tests the application of age estimation standards developed by the authors from a white population. All specimens were obtained from medical examiner's cases of known age, sex, and race. Although the sample was limited in both quantity and age range, analysis of the data revealed racial differences in both rate and pattern of metamorphosis. Statistical analysis showed that the calculated mean age per phase for black ribs was nearly identical to whites in Phases 1 through 4 or until the mean age of 28 years. By the early 30s, differences in morphology and their chronological association with the aging process became apparent and increased with age in both sexes. Blacks were consistently overaged from 3 to 10 years in Phases 5 through 7. Therefore, it was concluded that biological differences between these populations do exist and can affect age estimation from the rib. Social factors may also be involved, but they cannot be demonstrated from the available data. While the degree of interracial variation does not require completely new standards, the authors have suggested specific modifications of the white standards for use on black specimens.

Ifosfamide-induced subclinical tubular nephrotoxicity despite mesna.

We monitored acute tubular damage in 16 patients who received a 5-day course of ifosfamide (1.6 g/m2/day) and mesna (1.2 g/m2/day) therapy. Urinary concentrations of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein increased in every patient, but the extent of tubular toxicity varied widely among patients. Evidence of toxicity was greatest in patients whose tumors involved the kidneys. The time course of enzymuria and proteinuria indicated tubular cell necrosis. We observed this acute toxic effect despite the administration of sufficient mesna to prevent hemorrhagic cystitis. Urinary marker concentrations returned towards pre-dose levels, and there were no increases in serum creatinine concentrations measured 3 weeks after treatment.

Carboplatin (CBDCA), iproplatin (CHIP), and high dose cisplatin in hypertonic saline evaluated for tubular nephrotoxicity.

We compared the acute tubular nephrotoxicity of three platinum compounds in children and adults with solid tumors by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein. Cisplatin (100 mg/m2) was administered with mannitol, or at a twofold larger total dosage (50 mg/m2 per day for 4 days) in a 3% saline infusion. Carboplatin (300 mg/m2) was administered in combination with 5-fluorouracil, and iproplatin was administered in dosages ranging from 216 to 388 mg/m2. Enzymuria and proteinuria induced by cisplatin at a total dosage of 200 mg/m2 on a divided schedule did not significantly differ from that observed for the single 100 mg/m2 dose. Enzymuria and proteinuria induced by carboplatin and iproplatin were significantly less than that for cisplatin; however, one patient developed chronic tubular damage after three courses of carboplatin, and the acute tubular toxicity of iproplatin in one of 15 patients was exceptional. Our findings support the value of administering cisplatin in hypertonic saline on a divided schedule as a strategy to reduce acute tubular damage. Although carboplatin and iproplatin are less nephrotoxic than cisplatin, occasionally patients experience subclinical acute or chronic tubular damage that may lead to overt nephrotoxicity with continued therapy.

Cancer chemotherapy-induced tubular nephrotoxicity evaluated by immunochemical determination of urinary adenosine deaminase binding protein.

The authors evaluated measurements of adenosine deaminase binding protein (ADB), a proximal renal tubular cell antigen, for detection of drug-induced tubular nephrotoxicity. Concentrations of ADB were determined immunochemically in serial urine specimens from 12 children who were receiving chemotherapy for malignant solid tumors. There was no indication of increased ADB excretion after administration of two nonnephrotoxic drugs, etoposide and doxorubicin, but in patients given the recognized nephrotoxins, cisplatin and methotrexate, or an investigational drug, ifosfamide, urinary concentrations of ADB increased greater than fivefold relative to baseline values. Increased ADB concentrations preceded cisplatin- or ifosfamide-induced elevations of serum creatinine. Results of the ADB assay correlated well with those obtained by enzymatic assays for N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase (r = 0.76 and 0.53; n = 142, P less than 0.001) and marginally with total proteinuria (r = 0.21; P less than 0.02). Hence, serial ADB measurements may be useful in screening investigational drugs for acute subclinical nephrotoxicity.