PA CATHETER REDUCES MORBIDITY IN THE CRITICALLY ILL

The great controversy over the impact of the pulmonary artery (PA) catheter on patient outcome continues with new positive findings. This time, researchers have found that management strategies guided by this device reduce morbidity--a variable never before addressed in studies of PA catheters.

Ivanov et al performed a meta-analysis of 12 trials conducted from 1970 through 1996, involving a total of 1,610 patients. Previously, the researchers had found a trend toward reduced mortality when they studied these same data. In the new study, they found that the rate of major morbidity--defined as new organ failure--was significantly lower among patients treated with PA catheter--guided strategies than among controls (63% vs 74%; relative risk, 0.8). Furthermore, the same overall trend toward fewer complications among catheterized patients was found when the researchers looked at all types of morbidities.

"The implication of these findings is that … PA catheters, when used by protocol, [are] useful rather than harmful and that calls for a moratorium on their usage may be premature and unnecessary," Ivanov et al concluded.

Ivanov R, Allen J, Calvin JE. The incidence of major morbidity in critically ill patients managed with pulmonary artery catheters: a meta-analysis. Crit Care Med. 2000;28:615-619.

IL-2 INCREASES CD4 CELL COUNTS

The addition of interleukin-2 (IL-2) therapy to antiretroviral therapy for patients infected with the human immunodeficiency virus (HIV) increases CD4 cell counts significantly more than does antiretroviral therapy alone, according to a recent study. The effects of IL-2 were dose-dependent.

The trial involved 78 HIV-infected patients who were already receiving antiretroviral therapy, had never taken IL-2, and had never developed an AIDS-associated condition. The patients were randomized to antiretroviral therapy alone or to antiretroviral therapy plus intermittent IL-2 therapy. Six cycles of IL-2 were given as 7.5 mIU every 12 hours for five days, every eight weeks. The dose was reduced in patients experiencing serious adverse effects.

After one year of treatment, the IL-2 group showed a significantly greater average increase in CD4 cell counts than did patients taking antiretroviral therapy alone (112% vs 18%).

Patients who were able to tolerate higher doses of IL-2 had the greatest rise in CD4 cell counts (Figure 1).

Patients who received IL-2 also showed a small but significant decrease in viral load (mean change, --0.28 log10 copies), while patients given antiretroviral therapy alone had a slight increase in viral load. Viral suppression was achieved in a significantly greater proportion of the IL-2 group than in the group receiving antiretroviral therapy alone (67% vs 37%). "This is the first randomized controlled trial of IL-2 therapy demonstrating that IL-2 administered with potent [antiretroviral therapy] is associated with enhanced viral suppression," Davey et al noted.

Adverse effects associated with IL-2 included fever, fatigue, and myalgias. One patient developed thrombophlebitis, another had increased bilirubin levels, and a third had an acute exacerbation of mania. To avoid toxic effects, the researchers suggested that the IL-2 dosage may need to be adjusted in patients undergoing long-term therapy. "However," they concluded, "these toxic effects are largely predictable and do not diminish the rationale for selecting a starting dosage of proven efficacy in this range, especially since the CD4 cell response in this trial was strikingly dose-dependent."

Davey RT Jr, Murphy RL, Graziano FM, et al. Immunologic and virologic effects of subcutaneous interleukin-2 in combination with antiretroviral therapy: a randomized controlled trial. JAMA. 2000;284:183-189.

DIESEL EXHAUST CAUSES AIRWAY INFLAMMATION

Inhalation of particulate matter in diesel exhaust causes an inflammatory response in the airways of healthy people, Nightingale et al found in a randomized, crossover study. "The study gives direct evidence of an important role for the particulate fraction of diesel exhaust in provoking this inflammatory response in human subjects," the researchers believe.

Three men and seven women with normal lung function and bronchial reactivity were studied after two hours of exposure to diesel exhaust particles (200 µg/m3 particulate matter of less than 10 µm aerodynamic diameter) or clean air. After a four-week washout period, the subjects were exposed to the other test condition.

Peak levels of exhaled carbon monoxide were significantly higher after the diesel exhaust exposure than after the clean air exposure (4.4 ppm vs 2.9 ppm). Diesel exhaust exposure was also associated with significant increases in neutrophils (41% vs 32%) and myeloperoxidase (151 ng/mL vs 115 ng/mL) in induced sputum.

Cardiovascular parameters, lung function, and concentrations of inflammatory markers in peripheral blood were similar under both test conditions. "Unlike those in previous studies, our subjects did not complain of any adverse effects of symptoms from the exposure to [diesel exhaust particulates]," Nightingale et al noted.

Nightingale JA, Maggs R, Cullinan P, et al. Airway inflammation after controlled exposure to diesel exhaust particulates. Am J Respir Crit Care Med. 2000;162:161-166.

EXCESS WORKLOAD IN ICU LINKED TO MORTALITY

Patients treated in intensive care units (ICUs) with high workloads are more likely to die than are those treated in low-workload ICUs, new findings suggest. The high workloads "could reflect inadequate numbers of nursing or medical staff, training, supervision, or equipment," Tarnow-Mordi et al reported.

The researchers examined workloads per shift during 1,050 patients' stays at one Scottish ICU. Measures of workload included occupancy, the ICU nursing requirement (ie, the number of nurses required for the ICU as defined by the United Kingdom's Intensive Care Society), and the ratio of occupied to appropriately staffed beds.

The ICU was defined as full when six beds were filled, but frequently seven or eight patients were cared for in the unit.

Occasionally, an area in another part of the hospital was used to accommodate two or more ICU patients, raising the number of possible ICU beds to 10.

As shown in Table 1, mortality was affected by the interaction between the average nursing requirement per shift and peak occupancy. "We conclude that variations in hospital mortality may partly be explained by excess ICU workload," noted the authors. "These observations and this approach may have important implications for planning, risk management, and clinical governance," they added.

Tarnow-Mordi WO, Hau C, Warden A, Shearer AJ. Hospital mortality in relation to staff workload: a 4-year study in an adult intensive-care unit. Lancet. 2000;356:185-189.

GASTROESOPHAGEAL REFLUX: A CAUSE OF SINUSITIS?

Gastroesophageal reflux (GER) may contribute to the development of sinusitis in children, according to findings reported by Phipps et al. In this study, children with sinusitis refractory to medical treatment had a high prevalence of GER, and most improved following treatment for GER.

The researchers studied 30 consecutive children, age 2 to 18 years, who were referred for evaluation of chronic sinus disease. None of these patients responded to aggressive treatment with antibiotics or intranasal saline and nasal sprays. The researchers used 24-hour pH probes to evaluate the patients for GER and nasopharyngeal reflux. Patients with GER were treated with cisapride as well as a histamine2 blocker or proton pump inhibitor and diet modifications.

GER was found in 19 patients (63%). This prevalence is much higher than that expected in the general population (5%), according to Phipps et al. Six of the patients with GER (32%) also had nasopharyngeal reflux.

Fifteen of the 19 patients with GER (79%) improved following treatment for that condition. One child's symptoms remained unchanged despite treatment for GER, another did not comply with treatment, and a third had not been given therapy for GER. Follow-up information was missing for the fourth child.

The researchers recommended that children with chronic sinus syndrome that is refractory to aggressive medical management should be evaluated for GER. The authors found the pH probes used in their study were safe and well tolerated.

Phipps CD, Wood WE, Gibson WS, Cochran WJ. Gastroesophageal reflux contributing to chronic sinus disease in children: a prospective analysis. Arch Otolaryngol Head Neck Surg. 2000;126:831-836.

INADEQUATE TREATMENT OF BLOODSTREAM INFECTIONS

Inadequate antimicrobial treatment of bloodstream infections markedly increases the risk of death in intensive care units, according to a prospective study.

Of 4,913 consecutive patients admitted to the medical or surgical intensive care units at one hospital during a two-year period, 492 (10%) had bloodstream infections. A total of 147 (29.9%) of these 492 patients received inadequate antimicrobial treatment, meaning they did not receive an appropriate agent at the time the causative microorganism and its antibiotic susceptibility were determined.

Patients who received inadequate treatment had a significantly higher mortality rate than did those with adequate treatment (61.9% vs 28.4%). Inadequate antimicrobial treatment was the greatest independent risk factor for hospital mortality; patients with inadequate treatment were almost seven times more likely to die than were those with adequate treatment. (Factors associated with inadequate antimicrobial treatment are shown in Table 2.)

Also, patients with hospital-acquired bloodstream infections were significantly more likely to receive inadequate treatment than were patients with community-acquired bloodstream infections.

To balance the benefit of providing adequate antimicrobial treatment against the risk of unnecessary antibiotic treatment, Ibrahim et al recommended "early administration of broad-spectrum antimicrobial treatment to high-risk patients with suspected bloodstream infections." They added, "This should be followed by rapid tailoring of the antimicrobial regimen or discontinuation of antimicrobial treatment on the basis of culture results and the clinical course of the patient."

Ibrahim EH, Sherman G, Ward S, et al. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest. 2000;118:146-155.

RV DYSFUNCTION IN PULMONARY EMBOLISM

The presence of right ventricular (RV) dysfunction increases the risk of shock and in-hospital mortality among normotensive patients with pulmonary embolism (PE), according to a recent study. The findings suggest that these patients may require aggressive treatment.

Grifoni et al compared the outcomes of 65 normotensive patients with echocardiographic evidence of RV dysfunction and 97 normotensive patients without RV dysfunction. All patients were immediately started on intravenous heparin as soon as PE was suspected.

PE-related shock developed in six of the patients with RV dysfunction--three of whom died in the hospital--but in none of the patients without RV dysfunction. Echocardiographic signs of RV dysfunction had a sensitivity of 100%, a specificity of 61%, a positive predictive value of 5%, and a negative predictive value of 100% in predicting PE-related in-hospital mortality among normotensive patients.

The results suggest that "echocardiographic examination of normotensive patients with PE is mandatory for early detection of latent hemodynamic impairment, provides valuable information for risk stratification, and appears to be most relevant as a screening test for the identification of low-risk patients," reported Grifoni et al.

Grifoni S, Olivotto I, Cecchini P, et al. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation. 2000;101:2817-2822.

MINI-TRACHEOTOMY FOR SEVERE OBSTRUCTIVE SLEEP APNEA

A 2-mm tracheotomy, when combined with an airflow delivery device, is as effective as a large-tube tracheotomy in the treatment of severe obstructive sleep apnea. "Based on our clinical experience, we know that many people cannot use the [continuous positive airway pressure] mask but refuse to have a tracheotomy because they cannot stand the thought of having a big hole in their neck.… This study shows a new, potentially more tolerable approach," said lead author Alan Schwartz, MD.

The study involved five patients who had undergone large-tube tracheotomies. Caps were placed over the existing holes and a skinny tube was slipped through the cap to simulate a mini-tracheotomy. The patients were monitored for three nights.

The researchers found that a greater flow of air was needed to avoid apnea, so they administered high-flow transtracheal insufflation. However, the higher flow rate sometimes caused repetitive laryngeal obstructions and increased tracheal pressure as patients fell asleep. To avoid this problem, the researchers developed a computer-controlled flow delivery device that monitored tracheal pressure and varied the flow of air to keep this pressure below 20 cm H2O.

The high-flow system significantly lowered the frequency of obstructive apneas and hypopneas per hour (from 63.8 to 10.7). In addition, arousal frequency decreased from 67.5 to 0 per hour during rapid eye movement (REM) sleep and from 60.0 to 8.3 per hour during non-REM sleep with the new approach.

Schneider H, O'Hearn DJ, Leblanc K, et al. High-flow transtracheal insufflation treats obstructive sleep apnea: a pilot study. Am J Respir Crit Care Med. 2000;161:1869-1876.

OCCUPATIONAL ASTHMA AND HOSPITALIZATION RISK

Workers with occupational asthma are at higher risk for hospitalization than are those with musculoskeletal injury, new findings suggest. "Given that [occupational asthma] is preventable and that serious sequelae may develop, our findings underscore the need for greater attention directed toward primary prevention of this condition," according to Liss et al.

The researchers studied 844 workers with occupational asthma, 1,556 workers with musculoskeletal injury, and 402 asthma patients who attended an asthma clinic. The most common causes of occupational asthma were exposure to isocyanates (52%), flour (6%), and metals (4%). Other allergens included grains, plastics, non-cedar wood dust, welding fumes, paint, chlorine, and solvents.

The rate of hospitalizations for all causes was 47% for the asthma clinic patients, 39.2% for the occupational asthma patients, and 29.2% for the musculoskeletal injury group. Compared with the latter group, subjects with occupational asthma were significantly more likely to be hospitalized for all causes; most of this difference was attributable to the markedly higher rates of hospitalization for respiratory diseases and asthma in the occupational asthma group.

Occupational asthma patients were about half as likely as asthma clinic patients to be hospitalized for asthma and respiratory disease but were 30% more likely than asthma clinic patients to be admitted for ischemic heart disease. Factors associated with hospitalization for asthma in the occupational asthma group included exposure to agents other than isocyanate, nonsmoking status, and older age.

Interestingly, the risk of hospitalization for respiratory diseases declined markedly five or more years after the onset of symptoms in patients with occupational asthma. Liss et al believe that the effect of work-related sensitization might decline following diagnosis and removal of the causative agent.

Liss GM, Tarlo SM, MacFarlane Y, Yeung KS. Hospitalization among workers compensated for occupational asthma. Am J Respir Crit Care Med. 2000;162:112-118.

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