The importance of bacterial sepsis in intensive care unit patients with acquired immunodeficiency syndrome: implications for future care in the age of increasing antiretroviral resistance.

OBJECTIVE: To describe the clinical characteristics and outcomes of patients with acquired immunodeficiency syndrome (AIDS) admitted to the intensive care unit (ICU). DESIGN: An observational cohort study with retrospective chart review. SETTING: ICU of an urban university medical center. PATIENTS: Consecutive ICU admissions of patients with AIDS at an urban university medical center between December 1993 and June 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each patient, we recorded ICU admission diagnosis, clinical characteristics, and outcome. Among 129 ICU admissions of patients with AIDS, 102 (79%) were admitted for infections, of which (45%) had infections caused by bacteria. Pseudomonas aeruginosa, Staphylococcus aureus, and other enteric pathogens were the most frequent isolates. Pneumonia accounted for 65% of 102 admissions for infections. Overall hospital mortality was 54%, but mortality was higher (68%) for patients with bacterial sepsis. Neutropenia was associated with differences in unadjusted survival rates, whereas CD4 counts were not. Independent predictors of hospital mortality included increasing acute physiology scores and severity of sepsis. CONCLUSIONS: In our ICU, among patients with AIDS, sepsis resulting from bacterial infection is now a more frequent cause of admission than Pneumocystis carinii pneumonia. Severity of illness and the presence of severe sepsis were the clinical predictors most associated with increased mortality. Patients who are not receiving or responding to highly active antiretroviral therapy may become as likely to be admitted to an ICU with a treatable bacterial infection as with classic opportunistic infections. Therefore, broad-spectrum empirical antibacterial therapy is particularly important when the etiology of infection is uncertain.

The impact of long-term acute-care facilities on the outcome and cost of care for patients undergoing prolonged mechanical ventilation.

OBJECTIVES: To compare the 6-month mortality rate of chronically ventilated patients treated either exclusively in a traditional acute-care hospital or transferred during hospitalization to a long-term acute-care facility. To analyze the hospital cost of care and estimate the amount of uncompensated care incurred by acute-care hospitals under the Medicare prospective payment diagnostic related groups system. DESIGN: Retrospective chart review and questionnaire. SETTING: Fifty-four acute-care referral hospitals and 26 longterm acute-care institutions. PATIENTS: A total of 432 ventilated patients selected from 3,266 patients referred but not transferred to a study long-term acute-care facility and 1,702 ventilated patients from 4,174 patients referred and then subsequently transferred to the long-term acute-care facility. Six-month outcomes were determined for the subgroup of patients > or =65 yrs old (279 and 1,340 patients, respectively). Hospital charges were available for 192 of the 279 nontransferred patients who were > or =65 yrs old and 1,332 of the 1,340 transferred patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 6-month mortality rate was 67.4% for the 279 nontransferred patients and 67.2% for the 1,340 transferred patients. On multiple regression analysis, variables associated with the 6-month mortality rate included initial admitting diagnosis, age, the acute physiology score, and presence of decubitus ulcer. After controlling for these variables, there was no significant difference in 6-month mortality rate, but admission to the long-term acute-care facility was associated with a longer mean survival time. Average total hospital costs for the 192 nontransferred patients was $78,474, and estimated Medicare reimbursement was $62,472, resulting in an average of $16,002 of uncompensated care per patient. Estimated costs for the long-term acute-care facility admissions were $56,825. CONCLUSIONS: Patients undergoing prolonged ventilation have high hospital and 6-month mortality rates, and 6-month outcomes are not significantly different for those transferred to long-term acute-care facilities. These patients generate high costs, and acute-care hospitals are significantly underreimbursed by Medicare for these costs. Acute-care hospitals can reduce the amount of uncompensated care by earlier transfer of appropriate patients to a long-term acute-care facility.

Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group.

OBJECTIVE: To determine the therapeutic efficacy and safety of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in the treatment of patients with severe sepsis. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter trial with a planned, midstudy, interim analysis. SETTING: Ninety-one academic medical center intensive care units in North America and Europe. PATIENTS: Patients with severe sepsis or septic shock (n = 696) received standard supportive care and antimicrobial therapy for sepsis, in addition to rhIL-1ra or placebo. INTERVENTIONS: Patients were randomized to receive either rhIL-1ra (100 mg) or placebo (vehicle) by intravenous bolus, followed by a 72-hr continuous intravenous infusion of either rhIL-1ra (2.0 mg/kg/hr) or placebo. MEASUREMENTS AND MAIN RESULTS: The study was terminated after an interim analysis found that it was unlikely that the primary efficacy end points would be met. The 28-day, all-cause mortality rate was 33.1% (116/350) in the rhIL-1ra treatment group, while the mortality rate in the placebo group was 36.4% (126/346), yielding a 9% reduction in mortality rate (p = .36). The patients were well matched at the time of study entry; 52.9% of placebo-treated patients were in shock while 50.9% of rhIL-1ra-treated patients were in shock at the time of study entry (p = .30). The mortality rate did not significantly differ between treatment groups when analyzed on the basis of site of infection, infecting microorganism, presence of bacteremia, shock, organ dysfunction, or predicted risk of mortality at the time of study entry. No excess number of adverse reactions or microbial superinfections were attributable to rhIL-1ra treatment in this study. CONCLUSIONS: A 72-hr, continuous intravenous infusion of rhIL-1ra failed to demonstrate a statistically significant reduction in mortality when compared with standard therapy in this multicenter clinical trial. If rhIL-1ra treatment has any therapeutic activity in severe sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.

Evaluating laboratory usage in the intensive care unit: patient and institutional characteristics that influence frequency of blood sampling.

OBJECTIVES: To develop a predictive equation to estimate the frequency of blood drawing for intensive care unit (ICU) laboratory tests and to evaluate variations in ICU blood sampling practices after adjusting for patient and institutional factors. DESIGN: Prospective, inception, cohort study. SETTING: Forty-two ICUs in 40 hospitals, including 20 teaching and 17 nonteaching ICUs. PATIENTS: A consecutive sample of 17,440 ICU admissions, in which 14,043 blood samples were drawn for laboratory testing on ICU days 2 to 7. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient demographic, physiologic, and treatment data were obtained on ICU day 1; the type and number of blood samples for laboratory testing were recorded on ICU days 1 to 7. In the 42 ICUs, a mean of 16.2 blood samples were drawn for tests on ICU days 2 to 7, but varied between 23 samples in the teaching ICUs and 9.9 samples in nonteaching ICUs. Using only ICU day 1 patient data, we predicted the subsequent number of samples drawn on ICU day 2 (R2 = .26 across individual patients) and on ICU days 2 to 7 (R2 = .26 across individual patients). The most important determinants of the number of blood samples drawn on ICU days 2 to 7 were the ICU day 1 Acute Physiology Score and admission diagnosis. After controlling for patient variables, hospital teaching status, number of beds, and location in the East and South were significantly (p < .05) associated with increased blood sampling on ICU day 2 and on ICU days 2 to 7. More frequent use of an arterial cannula and mechanical ventilation were also associated with increased blood sampling on subsequent days. CONCLUSIONS: The ability to adjust for patient and institutional variables and to predict the number of blood samples drawn for laboratory tests can allow ICUs to compare their practices with those of other units. When integrated into a continuous quality improvement process, this information can be used to identify and focus on opportunities for improving blood conservation and reducing excessive diagnostic testing.

Predicting the duration of mechanical ventilation. The importance of disease and patient characteristics.

STUDY OBJECTIVE: To analyze the determinants of an individual patient's duration of mechanical ventilation and assess interhospital variations for average durations of ventilation. DESIGN: Prospective, multicenter, inception, cohort study. SETTING: Forty-two ICUs at 40 US hospitals. PATIENTS: A total of 5,915 patients undergoing mechanical ventilation on ICU day 1 selected from the acute physiology and chronic health evaluation (APACHE) III database of 17,440 admissions. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Utilizing APACHE III data collected on the 5,915 patients, multivariate regression analysis was performed on selected patients and disease characteristics to determine which variables were significantly associated with the duration of mechanical ventilation. An equation predicting duration of ventilation was then developed using the significant predictor variables and its accuracy was evaluated. Variables significantly associated with duration of ventilation included primary reason for ICU admission, day 1 acute physiology score (APS) of APACHE III, age, prior patient location and hospital length of stay, activity limits due to respiratory disease, serum albumin, respiratory rate, and PaO2/FIo2 measurements. Using an equation derived from these variables, predicted durations of ventilation were then calculated and compared with actual observed durations for each of the 42 ICUs. Average duration of ventilation for the 42 ICUs ranged from 2.6 to 7.9 days, but 60% of this variation was accounted for by differences in patient characteristics. CONCLUSIONS: For patients admitted to the ICU and ventilated on day 1, total duration of ventilation is primarily determined by admitting diagnosis and degree of physiologic derangement as measured by APS. An equation developed using multivariate regression techniques can accurately predict average duration of ventilation for groups of ICU patients, and we believe this equation will be useful for comparing ventilator practices between ICUs, controlling for patient differences in clinical trials of new therapies or weaning techniques, and as a quality improvement mechanism.

Intensive care unit admissions with cirrhosis: risk-stratifying patient groups and predicting individual survival.

Prognosis for acutely ill patients with cirrhosis is influenced by the severity of hepatic abnormalities and by dysfunction of other organ systems. The purpose of this study was to examine the usefulness of the Acute Physiology, Age, and Chronic Health Evaluation (APACHE III) prognostic system for risk-stratifying groups of intensive care unit (ICU) patients with cirrhosis and in predicting individual survival. We used data for 17,440 ICU admissions at 40 American hospitals to select 117 of the 537 patients with a history of cirrhosis who were ventilated on ICU day 1, a group known to have a high mortality rate. We then calculated each patient's probability of hospital death on ICU days 1 through 7, using seven previously validated multivariate equations. Hospital mortality was 63% for the 117 study patients. The most important determinants of risk for hospital death on ICU day 1 were the acute physiology score of APACHE III, ICU admission diagnosis, and operative status. Daily changes in the acute physiology score caused a rise or fall in the probability of hospital mortality and was useful in assessing individual response to therapy. APACHE III accurately risk stratifies critically ill patients with cirrhosis because it accounts for many of the factors known to influence prognosis. This capability can be used to assess severity of illness and risk-stratify patients with cirrhosis during clinical trials. Daily prognostic estimates based on physiological changes over time reflect patient response and can help physicians to assess the incremental benefit of therapy.

Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To describe outcomes and identify variables associated with hospital and 1-year survival for patients admitted to an intensive care unit (ICU) with an acute exacerbation of chronic obstructive pulmonary disease (COPD). DESIGN: Prospective, multicenter, inception cohort study. SETTING: Forty-two ICUs at 40 US hospitals. PATIENTS: A total of 362 admissions for COPD exacerbation selected from the Acute Physiology and Chronic Health Evaluation (APACHE) III database of 17,440 ICU admissions. MEASUREMENTS AND RESULTS: Hospital mortality for the 362 admissions was 24%. For the 167 patients aged 65 years or older, mortality was 30% at hospital discharge, 41% at 90 days, 47% at 180 days, and 59% at 1 year. Median survival for all patients was 224 days, and median survival for the patients who died within 1 year was 30.5 days. On multiple regression analysis, variables associated with hospital mortality included age, severity of respiratory and nonrespiratory organ system dysfunction, and hospital length of stay before ICU admission. Development of nonrespiratory organ system dysfunction was the major predictor of hospital mortality (60% of total explanatory power) and 180-day outcomes (54% of explanatory power). Respiratory physiological variables (respiratory rate, serum pH, PaCO2, PaO2, and alveolar-arterial difference in partial pressure of oxygen [PAO2-PaO2]) indicative of advanced dysfunction were more strongly associated with 180-day mortality rates (22% of explanatory power) than hospital death rates (4% of explanatory power). After controlling for severity of illness, mechanical ventilation at ICU admission was not associated with either hospital mortality or subsequent survival. CONCLUSIONS: Patients with COPD admitted to an ICU for an acute exacerbation have a substantial hospital mortality (24%). For patients aged 65 years or older, mortality doubles in 1 year from 30% to 59%. Hospital and longer-term mortality is closely associated with development of nonrespiratory organ system dysfunction; severity of the underlying respiratory function substantially influences mortality following hospital discharge. The need for mechanical ventilation at ICU admission did not influence either short- or long-term outcomes. Physicians should be aware of these relationships when making treatment decisions or evaluating new therapies.

Use of haloperidol infusions to control delirium in critically ill adults.

OBJECTIVE: To describe and discuss the use of continuous intravenous infusions of haloperidol to treat severe delirium and agitation in 3 intensive care unit (ICU) patients. CASE SUMMARIES: Three severely agitated patients in ICU did not respond to conventional therapy with opiates, benzodiazepines, and intermittent intravenous doses of haloperidol. In each case, control was achieved rapidly after initiation and titration of a continuous haloperidol infusion. Two patients had a history of schizophrenia. No adverse effects attributable to therapy were identified. DISCUSSION: Haloperidol is often used in the ICU for control of severe agitation, even in patients without a psychiatric history. It usually is given by bolus intravenous injection, sometimes in high doses (> 5 mg), even though that is not approved by the Food and Drug Administration. Intravenous haloperidol is generally well tolerated, but multiform ventricular tachycardia has been reported. Experience with continuous haloperidol infusions is growing, and it appears to be an effective method for control of severe agitation or delirium. In our experience and in other limited published data, adverse effects are rare, but prolongation of the QT interval has occurred and multiform ventricular tachycardia is likely a risk. CONCLUSIONS: In selected patients, a continuous infusion of haloperidol may be a useful alternative for control of agitation and delirium. Close monitoring for QT prolongation or rhythm disturbances is mandatory.

The use of APACHE III to evaluate ICU length of stay, resource use, and mortality after coronary artery by-pass surgery.

OBJECTIVE: To identify patient characteristics that are associated with increased ICU length of stay, resource use, and hospital mortality after coronary artery bypass surgery. DESIGN: Prospective, multicenter study. SETTING: Six tertiary care hospitals. PARTICIPANTS: A consecutive sample of 2,435 unselected ICU admissions following coronary artery by-pass surgery. MATERIALS AND METHODS: Demographic, operative characteristics and APACHE III score were collected during the first postoperative day; and APACHE III scores and therapeutic interventions during the first three postoperative days. Hospital survival and ICU length of stay were also recorded. Multivariate equations were derived and cross-validated to predict hospital mortality, ICU length of stay, and ICU resource use. RESULTS: Unadjusted hospital mortality rate was 3.9% (range 1.0% to 6.0%), mean ICU length of stay was 3.7 days (range 3.2 to 4.7 days), and first 3-day ICU resource use (TISS points) was 99 (range 68 to 116). The range of actual to predicted ICU length of stay varied from 0.86 to 1.26; and resource use from 0.71 to 1.16. CONCLUSIONS: A limited number of operative characteristics, the post-operative acute physiology score (APS) of APACHE III and patient demographic data can predict hospital death rate, ICU length of stay, and resource use immediately following coronary by-pass surgery. These estimates may compliment assessments based on pre-operative risk factors in order to more precisely evaluate and improve the efficacy and efficiency of cardiovascular surgery.

Facilitation of internal jugular venous cannulation using an audio-guided Doppler ultrasound vascular access device: results from a prospective, dual-center, randomized, crossover clinical study.

OBJECTIVE: To determine the utility of an audio-guided Doppler ultrasound device in improving success and decreasing complications in cannulation of the internal jugular vein in high-risk patients. DESIGN: Prospective, randomized, crossover clinical study. SETTING: Two major university medical centers in critical care environments. PATIENTS: Seventy-six consecutive, consenting adult patients with preexisting obesity or coagulopathy requiring central venous access. INTERVENTIONS: Subjects enrolled in the study were randomized to receive either the traditional "blind" (control) technique or the ultrasonic technique. A maximum of three cannulation attempts were allowed before crossover to three attempts with the alternative technique. All cannulations were attempted via the internal jugular vein through a high/central approach. RESULTS: Patient and operator characteristics were similar between groups. The initial use of an audio-guided ultrasound device was associated with increased success of cannulation (84.4% vs. 61.4%; p < .05) and decreased need to crossover to the alternative technique. Success on the first needle pass was more likely with the ultrasound technique (56.3% vs. 29.5%; p < .05). Significant complications were greater with the control technique (carotid artery puncture 16.3% vs. 2.0% [p < .02]; any significant complication 26.5% vs. 6.1% [p < .01]). CONCLUSIONS: The use of an audio-guided Doppler ultrasound vascular access device was associated with increased success of cannulation and a decreased frequency of significant complications in a population of high-risk patients with obesity or coagulopathy.

Use of femoral venous catheters in critically ill adults: prospective study.

OBJECTIVE: To determine the frequency of clinically important complications of femoral venous catheters. DESIGN: Prospective survey of major and minor complications. SETTING: A mixed medical/surgical ICU in a university hospital. PATIENTS: One hundred twenty-three patients admitted to the ICU who underwent femoral venous catheterization over a 2-yr period. MEASUREMENTS AND MAIN RESULTS: There were 150 catheters inserted in 123 patients for a mean duration of 6.4 days. There were no major complications including catheter-related sepsis. Minor complications consisted of arterial puncture (9.3%), local bleeding (10%), and local inflammation (4.7%). Critical care fellows had a significantly lower rate (6%) of insertion complications than interns or medical students (16%). We did not specifically look at the frequency of deep venous thrombosis. CONCLUSIONS: Femoral venous catheterization offers an alternative site of insertion to the subclavian and jugular veins for central venous access in the critically ill. The occurrence rate of clinically important complications is acceptably low.

Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability.

Theophylline overdoses are frequent conditions that may require emergency treatment. Clinical features common to severe theophylline toxicity include nausea and vomiting, tachydysrhythmias, metabolic disturbances, seizures, and cardiovascular collapse. Several reports have described these manifestations and their treatments. We report the case of a patient suffering from an acute, intentional theophylline overdose who exhibited the classic features of a toxic ingestion and describe the first reported use of IV esmolol in the treatment of accompanying cardiovascular manifestations.

Occult malignant neoplasm in patients with deep venous thrombosis.

An association between venous thrombosis and cancer was first suggested by Armand Trousseau and subsequently confirmed by multiple postmortem studies. In a previous study, patients with pulmonary embolism, as assessed by pulmonary angiography, were at significantly increased risk of occult cancer with a comparison group of patients without pulmonary embolism. This nonconcurrent prospective epidemiologic study extends these findings by demonstrating a significantly increased risk of occult cancer in patients with deep venous thrombosis (DVT) confirmed by impedance plethysmography as compared with those with suspected DVT in whom the diagnosis was ruled out. Differences in the incidence of malignant neoplasms were greatest within the first two years after the diagnosis of DVT, and patients younger than 50 years with venous thrombosis were at particularly increased risk of occult cancer (relative risk, 19.0). These findings indicate that all patients with DVT or pulmonary embolism should have an appropriate diagnostic workup and careful follow-up, particularly with regard to the risk of occult cancer.

Complications associated with thoracocentesis.

In order to determine the spectrum and frequency of complications associated with thoracocentesis, we decided to audit prospectively all thoracocentesis performed in the medical service at our institution. Over a ten-month interval, 125 procedures were performed. We identified 114 (91 percent) prospectively, 11 retrospectively by a computer-assisted review of discharge summaries. Forty-six percent of the procedures were complicated by at least one adverse occurrence. Complications considered major occurred in 14 percent, minor in 33 percent. The major complications included 14 pneumothoraces (three required tube thoracostomies and one percutaneous aspiration), one splenic laceration, one sheared-off catheter, and one pneumohemothorax. The minor complications included pain in 28, persistent cough in 14, dry taps in 16, and subcutaneous fluid collections in four patients. We conclude that thoracocentesis can carry the risk of frequent morbidity even when a lecture and printed guidelines on performing thoracocentesis have been given and experienced individuals are in attendance during the performance of the procedure. Our study suggests a portion of this morbidity may be from poor technique, inability to adequately identify landmarks, and improper utilization of a needle-catheter apparatus. Suggestions for correction of these problems are made.