Do not resuscitate orders and the cost of death.

BACKGROUND: The appropriate role of cardiopulmonary resuscitation in the hospital continues to be a topic of interest to physicians and patients alike. The use of do not resuscitate (DNR) orders reflects a growing expression of autonomy by patients to refuse medical treatment, and also a growing recognition of its futility in many circumstances by physicians. Although it has been suggested that wider use of advance directives will lead to a reduction in health care costs near the end of life, little empiric data exist to support this prediction. This study was designed to ascertain the rates of DNR orders and their associated costs. METHODS: A retrospective chart review was conducted on the hospital records of 852 of 953 hospital deaths that occurred in a referral hospital. Data were collected on resuscitation status, timing of DNR orders, participants in decision making, and physician and hospital charges. RESULTS: Of the 852 records reviewed, 625 (73%) had a DNR order at the time of death. The use of DNR orders for patients who died ranged from 97% of those on an oncology service to 43% of deaths on cardiology services. One hundred seven patients (17%) had the DNR order before admission. Of 512 patients who had a new DNR order in the hospital, approval was obtained from the patient in only 19%. Patients who died with a DNR order had longer hospital stays (median, 11.0 days) compared with those who died without a DNR order (6.0 days). The time from DNR order to death was 2 days overall with 2.0 days for medical patients and 1.0 day for surgical patients. Average charges for each patient who died were $61,215 with $10,631 for those admitted with a DNR order, and $73,055 for those who had a DNR order made in hospital. CONCLUSION: This study demonstrates high variability in the use of DNR orders between various medical and surgical services. These range from a high of 98% on an oncology service to a low of 43% on cardiology. Most patients have a DNR order at the time of death, but these typically occur late in the course of the hospital stay. Death in the hospital is costly and total hospital and professional charges are significantly lower when a patient is admitted with an established nonresuscitation order compared with those for whom a DNR is established while in the hospital. This study provides a basis against which to measure the impact of efforts such as the Patient Self-Determination Act of 1990 to increase the use of advance directives, as well as monitor their effect on health care expenditures.

Physician-ordered respiratory care vs physician-ordered use of a respiratory therapy consult service. Results of a prospective observational study.

OBJECTIVE: To assess the impact of a respiratory therapy consult service (RTCS) on practices and appropriateness of ordering respiratory care services. DESIGN: Nonrandomized prospective observational cohort study with concurrent controls. SETTING: Adult non-ICU inpatient wards of an academic medical center. PATIENTS: A convenience sample of 98 adult non-ICU inpatients at the Cleveland Clinic Hospital, representing 20 inpatient clinical services. Patients whose respiratory care plans were determined by respiratory care practitioners using sign and symptom-based algorithms to specify treatment comprised the treatment group (n = 51, respiratory therapy consult group). The nonconsult group (n = 47) were patients whose respiratory care plans were specified by their own physicians. INTERVENTION: Specification of the respiratory care plan by the RTCS vs by the physicians themselves. Use of the RTCS was at the discretion of the managing physician. OUTCOME MEASURES: Types and number of respiratory care treatments, length of hospital stay, costs of the respiratory therapy provided, appropriateness of respiratory care orders (based on comparison of the actual respiratory care orders with a reference respiratory care plan generated by a study investigator who was kept blind to the actual respiratory care plan), and adverse respiratory events. RESULTS: Patients for whom the RTCS was requested by their physicians had a greater severity of respiratory illness based on having a lower triage score, but were otherwise similar at baseline. Fewer initial orders for respiratory care were discordant with the reference algorithms in RTCS patients (15% +/- 26% [SD]) than in nonconsult patients (43% +/- 36%; p < 0.001), and a smaller fraction of RTCS patients received at least one discordant initial respiratory care order (37% vs 72%; p < 0.001). Though provided to sicker patients with longer lengths of hospital stay, RTCS-directed care incurred similar respiratory care costs per patient ($335.63 +/- $272.69 [RTCS] vs $349.06 +/- $273.27; p = 0.72). CONCLUSIONS: These results suggest that the RTCS can be an effective strategy to allocate respiratory care strategies appropriately while conserving the costs of providing respiratory care.

Prevention of chronic cerebral vasospasm in dogs with milrinone.

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms for the treated group, compared with the control group (98.28 +/- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively; P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

The effects of anabolic steroids and strength training on the human immune response.

The immune response was assessed in 13 competitive bodybuilders self-administering anabolic-androgenic steroids and ten competitive bodybuilders not administering these drugs. Laboratory assessment included the number and relative distribution of T-cells, T-helper/inducer cells, T-cytotoxic/suppressor cells, activated T-cells, lymphocyte transformation to the mitogens, pokeweed mitogen (PWM), phytohemagglutinin (PHA), Concanavalin-A (CON-A), Staphylococcus aureus Cowan strain I (SAC), serum immunoglobulins, and natural killer (NK) activity. There were no significant differences in T-cell subsets among steroid users and non-users, but lymphocyte transformation studies revealed that the anabolic-androgenic steroid-using group had enhanced proliferative ability to the B-cell mitogen, SAC, in comparison to non-bodybuilding controls. NK activity was significantly (P less than 0.05) augmented in the anabolic-androgenic steroid users but not in the non-using bodybuilders. Serum immunoglobulin levels, in particular IgA, were significantly (P less than 0.017) lower in the steroid-using group. Four of 13 steroid users and three of eight non-steroid-using bodybuilders had detectable antinuclear antibodies. These studies indicate that 1) anabolic-androgenic steroid use as practiced by contemporary athletes is a potent modulator of immune responsiveness and 2) autoantibodies are prevalent in strength-trained men even in the absence of anabolic steroid use.

Summary of results of 1991 ASFA apheresis survey. American Society for Apheresis.

As part of gathering data for its Networking Directory, the Registry/Directory Committee of the American Society for Apheresis solicited data on the types of apheresis procedures performed, equipment used, and diseases treated in the year 1991. In this voluntary solicitation of the 266 centers responding, 94% were from the United States. For those centers reporting exact numbers of procedures performed out of all institutions doing the procedures 48,221 therapeutic and 330,702 donor procedures were reported. The dominant type of equipment being used is the centrifugal type. For therapeutic procedures plasma exchange is the most prevalent procedure and for donor procedures it is plateletpheresis. For therapeutics, Guillain-Barre syndrome was the most prevalent disease treated by plasmapheresis and leukemias by cytapheresis. The survey methodology proved to be valuable in gathering the data on a voluntary basis. With subsequent surveys and refinement of its methodology the apheresis practices in the United States could be assessed quantitatively to provide information on the number and types of procedures being carried out. Such information is required to assess the impact of apheresis technology on health care, to project trends, and to review the cost impact of this technology.

The International Apheresis Registry: results of 1983 second pilot.

Results of the second pilot of the International Apheresis Registry for 1983 involving 37 centers on four continents are presented. This report is a follow-up of the initial pilot reported previously and includes the results of 37 additional centers reporting on 659 patients for a total of 5,780 treatments. The results were collected through a single-page questionnaire. Information gathered included patient demographics, medical history, treatment specifics (type, methodology, access type, anticoagulants, drugs), side effects, response, and payment provider. The data are grouped by regions (East, Europe, and North America). Analysis of the data identifies the regional differences in apheresis usage and treatment specifics, suggesting that an international view of apheresis is more representative of this therapeutic modality than national results, which are highly dependent on the local economics and available technology.

Serum Lp(a) level as a predictor of vein graft stenosis after coronary artery bypass surgery in patients.

Although the serum lipoprotein fraction Lp(a) has been associated with coronary artery atherosclerosis, its relationship to narrowing of saphenous vein grafts has not previously been elucidated. We therefore measured serum Lp(a) levels in 167 symptomatic patients undergoing cardiac catheterization who had had coronary artery bypass surgery 0.7 to 14.3 years earlier. Lp(a), total cholesterol, and total triglyceride levels were compared with the degree of saphenous vein graft stenosis to test for any association. Serum Lp(a) levels were significantly associated with the degree of stenosis of saphenous vein grafts (r = .24, p = .002). Mean Lp(a) levels (mg/dl) in the 135 patients with stenosis were almost double (32.0 +/- 32.7, mean +/- SD) those in the 32 patients with no graft stenosis (16.7 +/- 22.6; p = .002). Graft stenosis was not associated with previous myocardial infarction, hypertension, obesity, diabetes, or smoking. Serum cholesterol levels (mg/dl) were slightly higher in the stenosis group (251.3 +/- 69) than in the no-stenosis group (231.8 +/- 48.8), but the difference was of borderline significance (p = .06). A stepwise increase in mean Lp(a) was found in groups of patients with increasing vein graft stenosis. At a serum Lp(a) level of 31.6 mg/dl or above, 92% of the patients demonstrated vein graft stenosis. Thus, patients with elevated Lp(a) levels have an increased risk of developing saphenous vein graft stenosis after coronary bypass surgery.

Dietary influences on cardiovascular disease risk in anabolic steroid-using and nonusing bodybuilders.

Recent studies have described an association between high-risk lipoprotein profiles and anabolic steroid abuse by athletes. However, none have included a comprehensive evaluation of diet as a confounding variable. The risk of cardiovascular disease (CVD) and its associations with drug abuse, dietary patterns, and training regimens were evaluated in 18 steroid-using (SU) and 17 non-steroid-using (NSU; no history of drug use or greater than or equal to 1 year drug-free) male bodybuilders. CVD risk was also evaluated in 10 control males. Fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and HDL subfractions 2 and 3, low-density (LDL) and very-low-density (VLDL) lipoprotein cholesterol, apoproteins (APO) A-1 and B, and triglycerides (TG) were analyzed at baseline (greater than or equal to 6 months drug-free) and the peak of steroid self-administration in SU. NSU were tested at similar times. Baseline CVD risk factor ratios (TC/HDL) were elevated (greater than 4.97) in 44% of SU and 24% of NSU. When baseline LDL and HDL values were compared to National Cholesterol Education Program CVD risk guidelines, these percentages stayed the same. At the peak of steroid administration significant changes were observed in LDL (22% increase), HDL (63% decrease), HDL-2 (86% decrease), HDL-3 (54% decrease), and TC/HDL (85% increase). No similar measures were observed among NSU or controls. Diets of all bodybuilders were similar, and included a daily intake of 5739 (+/- 2500) kcal, 324 (+/- 163) g protein, 637 (+/- 259) g carbohydrate, 214 (+/- 109) g fat, 5 (+/- 8) g alcohol, 1413 (+/- 1151) mg cholesterol, and a P/S ratio of 0.6 (+/- 0.3). Significant relationships between dietary fats and serum lipids were observed in the NSU. Polyunsaturated fatty acids were correlated with TG and VLDL (r = 0.69; p = 0.01), and TC/HDL (r = 0.06; p = 0.04). Total fats were correlated with TG (r = 0.57; p = 0.05), HDL-3 (r = -0.62; p = 0.04), and VLDL (r = 0.57; p = 0.05), and saturated fats with HDL-3 (r = -0.59; p = 0.055). Diet was moderately associated with lipoproteins in SU, but steroids had a much greater influence on CVD risk. Despite disease promoting diets NSU had relatively average CVD risk that may be attributed to protective effects of rigorous training.

Backwashing procedure for on-line reuse of a plasma fractionator in cryofiltration.

During membrane plasma fractionation therapy there are reported incidences of membrane plugging requiring the corrective actions of either filter replacement or backwashing (BW) in order to continue the treatment. In this preliminary study, a simple BW procedure to allow for on-line reuse of the filter (Asahi AP06M) during the treatment was evaluated to assess its efficacy and safety in cryofiltration (CF). Evaluations were carried out on two patients treated for rheumatoid arthritis. Seven tests, each using 1 L or 2 L warmed saline as a BW solution were performed to evaluate the decrease of the transmembrane pressure (TMP) between just before and after backwashing and TMP change during cryofiltration procedures between before and after backwashing. Sieving coefficients of total protein, albumin, immunoglobulins (G, M, A), fibrinogen, and rheumatoid factor were also calculated at 1,000 ml plasma volume processed. Results showed statistically significant decreases of TMP from 300 mm Hg to 70 mm Hg between just before and after both backwashing procedures, and that there were no significant changes in the TMP increase during the cryofiltration procedure between pre- and post-BW. The protein sievings were not significantly affected by BW. The use of a second liter for rinsing did not reduce the inlet pressure further suggesting that 1 L BW was adequate. The accumulated solutes did not affect significantly the effective mean pore size. The BW procedure did not affect the overall patient safety during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein(a) is an independent risk factor for cardiovascular disease in hemodialysis patients.

BACKGROUND: Although serum lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis in the general population and Lp(a) levels are increased in hemodialysis patients, an association of Lp(a) with the risk of clinical events attributed to atherosclerosis has not been established in the chronic hemodialysis patient population. We therefore determined the association between Lp(a) levels and the risk of clinical events of presumed atherosclerotic etiology in a prospective study of an outpatient hemodialysis population. METHODS AND RESULTS: Lp(a) was measured by radioimmunoassay in a baseline cardiovascular disease risk assessment in a consecutive series of 129 hemodialysis patients. The relation between baseline Lp(a) and clinical events of presumed atherosclerotic etiology was determined during 48 months of follow-up. Hemodialysis patients had a median Lp(a) concentration that was approximately four times as high as the median Lp(a) concentration in normal controls and twice as high as the levels in controls with angiographic evidence of coronary artery disease [median Lp(a), 38.4 versus 16.9 mg/dl; p less than 0.001]. Baseline Lp(a) levels were no different in participants with or with no history of a previous clinical event at the time of the baseline examination. However, baseline Lp(a) concentration (p less than 0.001) and a history of atherosclerotic clinical events (p = 0.001) were associated with clinical events during the period of follow-up. In contrast, baseline serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, age, gender, race, or duration of hemodialysis were unrelated to this risk in the prospective study. Stepwise multiple logistic regression analysis demonstrated that serum Lp(a) concentration (p = 0.001) and the presence of a previous clinical event (p = 0.004) were the only independent contributors to the risk of a clinical event during the period of follow-up. CONCLUSIONS: Lp(a) is an independent risk factor for clinical events attributed to atherosclerotic cardiovascular disease in patients receiving chronic hemodialysis treatment of end-stage renal disease.

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study.

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

A prospective, randomized, blinded, and placebo-controlled trial of intraoperative intra-arterial urokinase infusion during lower extremity revascularization. Regional and systemic effects.

OBJECTIVE: This study was designed to evaluate the safety and regional and systemic effects of three doses of urokinase (UK) infused into the distal arterial circulation during routine operative lower extremity revascularization. METHODS: One hundred thirty-four patients were prospectively randomized to receive one of three bolus doses of UK (125,000, 250,000, or 500,000 U) or placebo (saline) infused into the distal circulation before lower extremity bypass for chronic limb ischemia. Regional (femoral vein) and systemic (arm) blood was sampled before drug infusion, prereperfusion, and postreperfusion, and systemic blood samples were obtained 2 hours postreperfusion. Assays evaluated plasma levels of fibrinogen, fibrin(ogen) degradation products (FDP), fibrin breakdown products (D-dimer and fragment B-beta 15-42), and plasminogen. Patients were monitored for clinically evident bleeding complications. The Wilcoxon rank-sum test was used to compare different drug doses with the placebo. RESULTS: Intraoperative bolus UK infusions produced no significant fibrinogen breakdown compared with placebo. There was a dose-related decline in plasminogen levels, which became significant at a dose of 500,000 U of UK (p < 0.001). There were dose-related increases in plasma FDP, which became significant at dose of 250,000 and 500,000 U (p < or = 0.005), and in plasma D-dimer, which were significant at all UK doses (p < 0.001). The changes in plasma fibrinogen and markers of fibrin breakdown were similar in the regional and systemic circulations. There was no increase in operative blood loss, blood replaced, or wound hematoma formation. There was an unexplained increased mortality in the placebo group (21.1% vs. 2.0%, p = 0.033). CONCLUSIONS: Intraoperative bolus UK infusion is safe, with no significant fibrinogen depletion or increased operative blood loss or wound hematoma formation. Dose-related plasminogen activation resulted in significant breakdown in cross-linked fibrin in the distal circulation. Intraoperative bolus UK infusion may be valuable as an adjunct in patients with chronic occlusive disease who are undergoing revascularization. Detailed randomized studies are indicated to establish clinical efficacy.