Improved oxygenation utilizing a prone positioner in patients with acute respiratory distress syndrome.

OBJECTIVES: (a) To determine whether placing patients with acute respiratory distress syndrome in the prone position by a light-weight portable support frame improves oxygenation, (b) whether one can determine which patients benefit from prone positioning, and (c) to determine an effective technique for prone positioning of patients. DESIGN: Prospective, controlled trial without blinding. SETTING: Medical intensive care units in two urban university-affiliated hospitals. PATIENTS: Fifteen patients meeting a standard definition for acute respiratory distress syndrome were studied prospectively. Each patient acted as his own control for purposes of comparison. INTERVENTION: Patients were assigned randomly to begin in either supine or prone positions. The positioning frame was used to turn patients from one position to the other, and oxygenation, ventilation, respiratory mechanics, and hemodynamics were measured. RESULTS: Significantly better oxygenation was seen in the prone positions than in the supine (P < 0.05). In the overall population there was a decrease in AaDO2 of 21 mmHg when the patients were placed prone. The groups were then divided into responders (n = 9) and nonresponders (n = 6). There were significant differences between the groups (but not between positions) regarding PaO2, baseline, PaCO2, pulmonary artery pressures, and peak inspiratory pressures on the ventilator and in ICU length of stay and time on mechanical ventilatory support. CONCLUSION: Prone positioning improves oxygenation in the majority of patients studied and can be achieved relatively easily.

Accuracy of estimated creatinine clearance in obese patients with stable renal function in the intensive care unit.

We compared agreement between creatinine clearance values in obese, critically ill patients calculated using three common empirically derived formulas and modifications thereof, with creatinine clearance obtained by conventional 24-hour urine collection. We selected the charts of 22 patients in intensive care units (86% medical, 14% surgical) according to the following criteria: actual body weight greater than 150% of ideal body weight; serum creatinine variation of less than 15% from the day of starting 24-hour urine collection to the day before or after the collection; presence of a urinary bladder catheter; no history of renal dialysis; and clinical indication for renal function assessment. Mean measured 24-hour urinary creatinine clearance for all patients was 72 +/- 64 ml/minute (range 8-248 ml/min). The method of estimating creatinine clearance that showed the least mean bias was the equation of Salazar and Corcoran using a corrected serum creatinine concentration (mean bias -2 ml/min); however, the corresponding 95% confidence intervals were wide (-133-129 ml/min). The narrowest range of 95% confidence intervals were seen with Jelliffe's equation (mean bias 25 ml/min, 95% confidence intervals -41-90 ml/min). In this sample, estimated creatinine clearances did not agree acceptably with measured values. Despite low mean bias values, none of the empirically derived equations that we studied had clinically acceptable 95% confidence intervals. We recommend using the 24-hour urine collection method when assessing creatinine clearance in obese, critically ill patients.

IL-1ra administration does not improve cardiac function in patients with severe sepsis.

PURPOSE: The purpose of this study was to investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on myocardial function in septic patients. MATERIALS AND METHODS: A subgroup of patients from a prospective, randomized, double-blind, placebo-controlled, multicenter trial was studied from 63 academic medical centers in the United States, Canada, and Europe. A subgroup of 71 patients with severe sepsis in whom vasoactive support was little altered during the study was included. The patients were randomized to receive either placebo (n = 29) or IL-1ra at a dose of 1 mg/kg/h (n = 20) or 2 mg/kg/h (n = 22). RESULTS: Hemodynamic measurements were taken at baseline, and 1, 2, 3, 4, 8, and 12 hours after placebo or IL-1ra administration. No significant differences in hemodynamic parameters were observed between the groups or over time during the study period. CONCLUSIONS: IL-1ra administration has no effect on cardiac function in septic patients.

Effect of calcium replacement on the hemodynamic changes associated with high dose interleukin-2 therapy.

Administration of high-dose IL-2 results in hemodynamic changes that are similar to those seen in septic shock. These include a decrease in systemic vascular resistance (SVR) with a resultant drop in mean arterial pressure (MAP). Hypocalcemia is seen in septic shock and with IL-2 administration. Calcium replacement in septic shock has been reported to result in hemodynamic improvement; we therefore administered calcium to patients receiving high dose IL-2 to correct ionized hypocalcemia. Five consecutive patients underwent invasive hemodynamic monitoring before and during IL-2 administration. Calcium chloride was administered to correct ionized hypocalcemia, and hemodynamic parameters were monitored before and after calcium administration. Ionized hypocalcemia was associated with an elevation in parathyroid hormone levels. There was no toxicity related to the administration of calcium. An improvement in the MAP and SVR was seen early and late (after a dose of IL-2 was held) in the IL-2 treatment cycle; there were minimal effects at other points. Because of the potential hemodynamic benefit of calcium replacement, we recommend that ionized hypocalcemia be corrected in patients receiving high-dose IL-2.

Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer.

The immunoconjugate XMMCO-791/RTA consists of ricin A chain bound to a murine monoclonal antibody MoAb 791T. This monoclonal antibody (MoAb) binds to a glycoprotein of 72 kD, which is expressed on human colorectal carcinoma, ovarian carcinoma, and osteogenic sarcoma. XMMCO-791/RTA was tested in a Phase I trial with proposed dose escalation steps of 0.02, 0.04, 0.15, and 0.2 mg/kg per day. Twelve patients with metastatic colorectal carcinoma were treated at 0.02, 0.03, and 0.04 mg/kg per day dose levels administered over 1 hour on days 1-5. Study-related toxicities were hypotension (6 patients); greater than 10% weight gain (6 patients); peripheral edema (9 patients); fever (4 patients); confusion (3 patients); diarrhea (3 patients); proteinuria, as identified by dipstick (3 patients), greater than 0.6 mg/dl decrease in serum albumin (11 patients); greater than 25% decrease in oncotic pressure (10 patients), and a decrease in ionized calcium (8 patients). Six patients received a second course of treatment. HAMA levels developed in 9 patients and titers increased with number of courses administered. Decreased overall toxicity, in comparison to the first course, was noted, but one patient had an allergic-type response (hypotension, crushing chest pain, diaphoresis) after the test dose of the second course (HAMA level > 10,000 IgG). Life-threatening toxicity in the form of fluid shift, resulting in noncardiac pulmonary edema and third-spacing occurred after course 1 in 1 of 3 patients at the 0.04 mg/kg per day level. No further dose escalation was attempted and no antitumor activity was seen.

Introduction of a new tracheostomy exchange device after percutaneous tracheostomy in a patient with coagulopathy.

Presented is a case of a 22-year-old male bone marrow transplant recipient who developed severe methotrexate-induced oropharyngeal mucositis and respiratory insufficiency caused by sepsis. Coagulopathy and severe thrombocytopenia precluded surgical tracheostomy; however, dilatational percutaneous tracheostomy was performed uneventfully. The tracheostomy tube was later changed using a newly developed exchange device permitting intraprocedural oxygenation and stomal redilatation. We conclude that severe thrombocytopenia and coagulopathy are not an absolute contraindication for percutaneous tracheostomy and that the new tracheostomy exchange device optimizes airway management and safety during this procedure.

A study of proactive ethics consultation for critically and terminally ill patients with extended lengths of stay.

OBJECTIVE: To assess the effect of proactive ethics consultation on documented patient care communications and on decisions regarding high-risk intensive care unit (ICU) patients. DESIGN: Prospective, controlled study. PATIENTS: Ninety-nine ICU patients treated with >96 hrs of continuous mechanical ventilation. INTERVENTIONS: Three groups were compared: a) a baseline group enrolled in the study prior to the establishment of the hospital's ethics consultation service; b) a control group where ethics consultation was at the option of the care team; and c) a treatment group where the ethics service intervened proactively after patients received >96 hrs of continuous mechanical ventilation. Patient care planning, for subjects in the proactive group, was reviewed with physicians and with the care team using a standardized set of prompting questions designed to focus discussion of key decision-making and communication issues for critically and terminally ill patients. Issues and concerns were identified and action strategies were suggested to those in charge of the patient's care. Formal ethics consultation, using a patient care conference model, was made available upon request. MEASUREMENTS AND MAIN RESULTS: Post discharge chart reviews of the three groups indicated no statistically significant differences on important demographic variables including age, gender, and acuity. Comparisons of survivors and nonsurvivors for the three groups indicated, at statistically significant levels, more frequent and documented communications, more frequent decisions to forego life-sustaining treatment, and reduced length of stay in the ICU for the proactive consultation group. CONCLUSION: Proactive ethics consultation for high-risk patient populations offers a promising approach to improving decision-making and communication and reducing length of ICU stay for dying patients.

Complications of vascular catheterization in the critically ill. A prospective study.

Invasive hemodynamic procedures are increasingly used for monitoring critically ill and injured patients. The results of a prospective study on complications of 210 vascular catheterizations in 116 critically ill patients are reported. A total of 80 central venous (CV), 71 pulmonary artery (PA), and 59 arterial (A) catheterizations were performed during an interval of 6 months. Catheters were inserted by percutaneous techniques for all but seven of the procedures. CV catheters were associated with complications in 3.7%. However, complications were encountered in 10% of the PA catheterizations and 13.5% of systemic A catheterization. It appears that in a group of patients with observed hospital mortality of 36%, invasive monitoring is associated with a significant complication rate.

Cervical cytology and other screening methods among women admitted to the medical intensive care unit.

OBJECTIVE: This study was conducted to determine whether routine gynecologic screening is obtained for women admitted to a medical intensive care unit in a large tertiary medical center and whether this history is used to document and update screening for these patients. METHODS: A retrospective chart review of 65 women admitted to the medical intensive care units of Harper Hospital or Detroit Receiving Hospital of the Detroit Medical Center over a period of one month. RESULTS: None of the patients eligible for cervical cytology and pelvic examination had these issues addressed in the intake history or had any of the reviewed examinations done or planned for after discharge from intensive care. CONCLUSIONS: Admission to intensive care is an opportunity to assess and update routine gynecologic health screening. This important function is not routinely addressed in the medical records of women admitted to intensive care.

Expression of Q227L-galphas in MCF-7 human breast cancer cells inhibits tumorigenesis.

The effects of expression of mutant (Q227L)-activated Galphas and elevation of cAMP on mitogen-activating protein kinase (MAPK) activity and the transformed phenotype were studied in the MCF-7 human mammary epithelial cell line. Elevation of cAMP partially inhibited the epidermal growth factor-stimulated DNA synthesis and the intrinsic MAPK (ERK-1 and ERK-2) of serum-starved MCF-7 cells. Addition of 8Br-cAMP or expression of mutant (Q227L)-activated Galphas in MCF-7 cells blocked the ability of these cells to grow in an anchorage-independent manner, as assessed by colony formation in soft agar. 8Br-cAMP in the culture medium also blocked estrogen stimulation of MCF-7 cell proliferation in vitro. MCF-7 cells expressing Q227L-Galphas grew very slowly in vitro, and when these cells were injected s.c. into athymic mice implanted with estrogen pellets, the frequency of tumor formation was reduced greatly and the sizes of the tumors formed were much smaller than those in mice injected with MCF-7 cells that had been transfected with the empty vector. These results indicate that the intracellular levels of cAMP in transformed mammary epithelial cells can be a crucial factor in determining the expression of the transformed phenotype. Interactions between the Gs/adenylyl cyclase and MAPK-1,2 signaling pathways could be one mechanism by which expression of the transformed phenotype in mammary epithelial cells are regulated.

Diagnosis of acute diffuse pulmonary infiltrates in immunosuppressed patients by open biopsy of the lung.

Herein is a review of the results of open biopsies of the lung performed upon immunosuppressed patients between the years 1982 and 1988. The goal was to assess the safety and value of the procedure on a group of patients who are many times in extremis because of multiorgan failure. Obtaining the correct diagnosis and establishing treatment poses a challenge. The study includes 74 patients. Fifty-four had malignant tumors; 20 had various diseases associated with immunosuppression. The biopsy was obtained from the left side in 65 instances. An adequate thoracotomy was done to permit exploration of the thoracic cavity and obtain a representative sample of tissue. The mortality rate related to the operation was 1.4 percent and the complication rate was 11.0 percent. Forty-six percent of the infiltrates were the result of infection. In 42 percent, a change in treatment was made. Thirty-two percent survived and were discharged from the hospital. Patients with adverse drug reaction, with nonspecific pneumonitis and with bacterial infection had a favorable prognosis and benefited most from open biopsy of the lung.

The evolution of functional endoscopic sinus surgery in the Commonwealth of Virginia.

This is the largest retrospective analysis of sinus surgery ever reported involving 5,860 surgical as well as 6,769 diagnostic sinus procedures during a six year period, 1988-1993. During this time interval, the frequency of endoscopic procedures has increased dramatically. Because of the increased frequency of this procedure, we see the need for strict definition of the clinical indications for surgery for patients with chronic or acute sinusitis. In addition, the number of open procedures, namely the Caldwell-Luc procedure, as a treatment for sinusitis remained relatively constant despite the frequent use of endoscopic technique. Because of the endoscopic surgery's increased acceptance and advantages over the open surgical technique, we emphasize the need for continuing educational programs to train surgeons to perform the endoscopic procedure or referral of the patient to an otolaryngologist experienced in this technique.