PSEUDOMONAS AERUGINOSA BACTEREMIA IN CANCER PATIENTS

The frequency of Pseudomonas aeruginosa bacteremia is decreasing among cancer patients with solid tumors but has not changed among those with acute leukemia, Chatzinikolaou et al found in their review of patient records from 1991 to 1995. The data further suggest that "antibiotic regimens for empirical therapy of neutropenic patients and especially patients with acute leukemia should still provide coverage against P aeruginosa."

The researchers identified 245 episodes of P aeruginosa bacteremia in 240 patients hospitalized in a cancer center from 1991 to 1995. The incidence of P aeruginosa bacteremia during this five-year period was lower than that found in a study conducted at the same institution from 1972 to 1981 (2.8 vs 4.7 cases per 1,000 admissions). The infection was most common among patients with acute leukemia. In fact, P aeruginosa bacteremia was found 27 times more frequently among patients with acute leukemia than among patients with solid tumors.

While P aeruginosa bacteremia is usually thought to be a hospital-acquired infection, half of the patients were not in the hospital when they developed the infection. Thus, "physicians caring for patients with cancer cannot conclude that infection is unlikely to be due to P aeruginosa simply because the patient developed infection while in the community," Chatzinikolaou et al suggested.

The overall cure rate in this study was 80%, which is significantly higher than that found in the previous study (62%). In addition, cure rates were similar among patients treated with ß-lactam monotherapy and patients treated with a combination therapy.

Among acutely neutropenic patients, the cure rate was higher for those whose neutrophil counts rose above 0.10 X 10⁹/L during therapy than among patients whose counts remained below this level (97% vs 62%, respectively). The cure rate was also higher among patients with solid tumors (82%) than among patients with acute leukemia (77%). In contrast, the cure rate was lower among patients with shock (60% vs 86% for no shock) or pneumonia (63% vs 92% for no pneumonia).

Temperature was also related to cure rate; patients with temperatures between 38.3°C and 40.0°C had the highest cure rate (84%), while patients with temperatures of 37.0°C or less had the lowest rate (25%). In addition, the cure rate was higher when patients were treated early after the onset of infection.

Chatzinikolaou I, Abi-Said D, Bodey GP, et al. Recent experience with Pseudomonas aeruginosa bacteremia in patients with cancer: retrospective analysis of 245 episodes. Arch Intern Med. 2000;160:501-509.

TEST PREDICTS OUTCOME OF SEPTIC SHOCK

A short corticotropin stimulation test has good prognostic value for patients in septic shock, according to findings reported by Annane et al.

The study investigators prospectively evaluated the incidence of occult adrenal insufficiency among 189 septic shock patients. Plasma cortisol levels were measured before and at 30 and 60 minutes after a short corticotropin stimulation test was performed.

After 28 days of follow-up, 58% of the patients had died. The following factors were independent predictors of mortality: McCabe/Jackson score above 0, more than two organ system failures, arterial lactate level above 2.8 mmol/L, PaO2/FiO2 ratio of 160 mm Hg or less, baseline cortisol level above 34 µg/dL, and cortisol response to corticotropin of 9 µg/dL or less.

The findings showed three different survival patterns (Table 1). Annane et al concluded that the short corticotropin stimulation test should help in "identifying a group of patients at high risk of death and in planning new randomized trials, particularly to evaluate the effectiveness of corticosteroids."

Annane D, Sébille V, Troché G, et al. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA. 2000;283:1038-1045.

PRESEDATION GLASGOW COMA SCALE SCORE IS BEST

When sedation prevents an accurate recording of the Glasgow Coma Scale (GCS) score, the presedation score is preferable to the common practice of assuming a normal GCS value in calculating severity of illness or mortality predictions, Livingston et al have reported.

The researchers prospectively studied 13,291 patients consecutively admitted to intensive care units in Scotland. An APACHE II or APACHE III score was calculated to determine the probability of death. Among patients whose GCS scores could not be accurately measured in the first 24 hours following hospital admission, the APACHE scores were calculated in two ways: first, assuming the GCS score was normal and second, using the presedation GCS score.

Overall, 50% of the subjects required sedation during the first 24 hours. In 40% of these sedated patients, the presedation GCS score was lower than the normal value of 15, and use of the presedation score significantly improved mortality predictions. Interestingly, this effect was greatest in patients with a neurologic or trauma diagnosis but was also found in most diagnostic groups.

Use of the presedation GCS score eliminates "one possible source of error" in predicting outcome, the study investigators concluded.

Livingston BM, Mackenzie SJ, MacKirdy FN, Howie JC. Should the pre-sedation Glasgow Coma Scale value be used when calculating Acute Physiology and Chronic Health Evaluation scores for sedated patients? Crit Care Med. 2000;28:389-394.

DIAGNOSING ALCOHOL-RELATED SEIZURES

Carbohydrate-deficient transferrin (CDT) may aid in the overall diagnostic investigation of seizures but is not recommended as a marker for alcohol-related seizures on its own, according to a report by Bråthen et al.

While previous findings have suggested that CDT is a specific marker of sustained alcohol misuse, the validity of using CDT to detect alcohol-related seizures had not been examined. This study compared the utility of CDT with other biomarkers and clinical examination in the diagnosis of sustained alcohol misuse among 158 patients who had been hospitalized for seizures. The alcohol use disorders identification test (AUDIT) was considered the gold standard for diagnosis of alcohol misuse.

Overall, 53 patients (34%) were determined to have had alcohol-related seizures, according to AUDIT results. In comparison, CDT analysis had a sensitivity of 41% and a specificity of 84%. Interestingly, the sensitivity of CDT analysis was markedly higher in men than in women.

In addition to CDT, other biomarkers analyzed by the researchers included gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, the ratio of aspartate aminotransferase to alanine aminotransferase, and ethanol. Of these, CDT was the best single biomarker for alcohol misuse. However, the clinicians' evaluations of which seizures were alcohol-related had a greater accuracy than any biomarker.

Nevertheless, many cases were missed by the clinicians. Bråthen et al believe that "the high specificity of an increased CDT clearly indicates that this index may be a useful supplement to a thorough clinical evaluation of seizures with an obscure etiology."

The investigators also noted that CDT concentrations were significantly increased among patients taking enzyme-inducing antiepileptic drugs who abstained from alcohol. In fact, 38% of patients with false-positive results were taking these antiepileptic drugs.

Bråthen G, Bjerve KS, Brodtkorb E, Bovim G. Validity of carbohydrate deficient transferrin and other markers as diagnostic aids in the detection of alcohol related seizures. J Neurol Neurosurg Psychiatry. 2000; 68:342-348.

INTERLEUKIN 6 MAY BE AN EARLY MARKER OF INJURY SEVERITY

Interleukin 6 (IL-6) level may be a useful tool in determining the extent of injury following major trauma. Findings from a recent study showed that IL-6 concentrations increased immediately after trauma, and the magnitude of this increase corresponded with the severity of injury.

Gebhard et al prospectively examined serial blood samples taken from 94 trauma patients. Blood was obtained immediately at the scene of the unintentional injury before cardiopulmonary resuscitation was performed, and again upon hospital arrival, at 30 minutes after hospital arrival, every other hour during the first 12 hours, at 24 hours, and every other day thereafter.

IL-6 levels were elevated immediately after the injury, regardless of injury type. These levels were higher among patients with severe injuries (as determined by Injury Severity Score) than among patients with less severe injuries. In fact, Injury Severity Scores were significantly correlated with IL-6 levels at hospital admission and six hours later. After the first six to 12 hours of hospitalization, IL-6 concentrations decreased in all patients.

Gebhard et al also found a strong correlation between the highest IL-6 concentrations and the maximum levels of C-reactive protein, a substance associated with the extent of tissue damage. Because the release of IL-6 preceded the release of C-reactive protein by at least 12 hours, the researchers suggested that IL-6 may serve as an early marker of injury severity.

Gebhard F, Pfetsch H, Steinbach G, et al. Is interleukin 6 an early marker of injury severity following major trauma in humans? Arch Surg. 2000;135:291-295.

OPIOID ANALGESICS: INCREASED USE, DECREASED ABUSE

The increasing medical use of opioid analgesics to treat severe pain does not appear to be raising the rate of opioid abuse, according to the results of a study conducted by Joranson et al.

The findings are based on a retrospective survey of data on medical opioid use from the Automated Reports and Consolidated Orders System as well as data on opioid abuse from hospital emergency departments in the Drug Abuse Warning Network. Data from both sources were collected for the years 1990 to 1996. The researchers specifically focused on trends pertaining to five Schedule II opioids: fentanyl, hydromorphone, meperidine, morphine, and oxycodone.

The total number of opioid abuse reports per year remained low during the study period (32,430 in 1990 and 34,563 in 1996). Almost all of the five Schedule II opioids showed an increased rate of medical use and a decreased rate of medical abuse (Table 2).

Furthermore, although the total number of opioid abuse reports per year increased by 6.6% during the study period, the proportion of yearly opioid abuse reports to total drug abuse reports decreased by 25%. Thus, "compared with other drugs, illicit drugs in particular, the abuse of opioid analgesics appears to be relatively low," Joranson et al explained. "To maintain this trend, manufacturers, pharmacies, clinicians, and patients should continue their efforts to improve pain management while exercising care so that the diversion of opioid medications for non-medical use is minimized," the researchers added.

Joranson DE, Ryan DM, Gilson AM, Dahl JL. Trends in medical use and abuse of opioid analgesics. JAMA. 2000;283:1710-1714.

ACUTE RENAL FAILURE TIMING DOES NOT PREDICT SURVIVAL

The delayed occurrence of acute renal failure (ARF) during a patient's stay in the intensive care unit (ICU) is not an independent predictor of death, findings from a new study suggest.

Guerin et al prospectively examined all patients (n = 1,086) who presented with or later developed ARF at 28 multidisciplinary ICUs. These patients were divided into three groups based upon onset of ARF:

• Group A presented with ARF on ICU admission or during the first two days of ICU stay (68%).
• Group B developed ARF on days 3 to 6 (19%).
• Group C developed ARF on day 7 or after (13%).

The overall mortality rate was 66%. This rate increased significantly with later onset of ARF: mortality was 61% for group A, 71% for group B, and 82% for group C.

The following variables were independently associated with survival: age, Simplified Acute Physiology Score II on ICU admission, number of ARF episodes, McCabe/Jackson score, oliguria, hemodialysis, and ischemic acute tubular necrosis. In contrast, the timing of ARF onset was not an independent predictor of survival after the researchers controlled for these confounding factors.

According to Guerin et al, the increase in mortality rate with later onset of ARF is due to two phenomena: first, patients in groups B and C developed ARF during their ICU stay--indicating that their conditions worsened; and second, patients in groups B and C presented with cardiovascular dysfunction and infection more frequently than did patients in group A.

Guerin C, Girard R, Selli J-M, et al. Initial versus delayed acute renal failure in the intensive care unit. Am J Respir Crit Care Med. 2000;161:872-879.

INCREASING GASTRIC INTRAMUCOSAL pH IS NOT USEFUL

Therapy aimed at correcting low gastric intramucosal pH (pHi) in critically ill patients does not improve outcome, a new study has shown. The failure of treatment to improve outcome may be caused by an "inability to produce a clinically significant change in pHi or because pHi is simply a marker of disease rather than a factor in the pathogenesis of multiorgan failure," suggest Gomersall et al.

These authors examined 210 patients who were admitted to an intensive care unit (ICU) on an emergency basis. All patients underwent appropriate resuscitation maneuvers (to achieve prespecified targets) and then were randomized to a control or intervention group. In the intervention group, patients with a pHi of less than 7.35 after achieving the resuscitation targets or after receiving maximal therapy to achieve the targets were given additional colloid, followed by a dobutamine infusion of 5 to 10 µg/kg/min titrated against pHi. This treatment was continued for 24 hours.

In both groups, low pHi at admission was associated with a poor outcome. While the intervention significantly raised pHi levels among patients with a low pHi at admission (from 7.15 to 7.22), it did not improve outcomes. The groups showed similar rates of the following measurements: ICU mortality, hospital mortality, and 30-day mortality; survival curves; multiorgan dysfunction score; duration of ICU stay; and duration of hospital stay.

Gomersall CD, Joynt GM, Freebairn RC, et al. Resuscitation of critically ill patients based on the results of gastric tonometry: a prospective, randomized, controlled trial. Crit Care Med. 2000;28:607-614.

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