George Dimopoulos

Disseminated Aspergillosis in Intensive Care Unit Patients: An Autopsy Study

Abstract Disseminated aspergillosis is an uncommon but frequently fatal disease in critically ill populations. With studies suggesting that the incidence of this disease is increasing, and with relatively few epidemiological data available in this population, we evaluated cases of disseminated aspergillosis identified at autopsy over a one-year period on a 31-bed mixed medico-surgical intensive care unit (ICU) of an academic university hospital. In 1999, there were 489 deaths out of 2984 ICU admissions, and 222 autopsies were performed. Post-mortem examination demonstrated disseminated aspergillosis involving non-contiguous organs in 6 (2.7%) autopsies and, of these, five patients (2.3% of total) had had chronic obstructive pulmonary disease (COPD) and had been treated with corticosteroids and mechanical ventilation for pulmonary infection. One patient also had granulocytopenia. In each patient, sputum and bronchoalveolar lavage (BAL) cultures had been positive for Aspergillus fumigatus after ICU admission but this was considered as colonization and the patients were given fluconazole for suspected candidal infection. In conclusion, COPD patients treated with corticosteroids and presenting with pulmonary infection should be considered at risk for disseminated aspergillosis. The rapidly fatal outcome after ICU admission suggests that colonization with Aspergillus can occur before ICU admission.

Are infections due to resistant pathogens associated with a worse outcome in critically ill patients

OBJECTIVES To evaluate the outcome of critically ill patients infected with antimicrobial resistant microorganisms, and to analyse the factors involved in the development of antimicrobial resistance. METHODS All patients admitted to a 31-bed mixed medico-surgical intensive care unit who developed a nosocomial infection were prospectively followed until discharge or death. RESULTS Of 949 consecutive patients admitted, 186 developed a nosocomial infection: 79 with an antimicrobial-resistant pathogen and 107 with susceptible strains. The lungs were the main source of infections in both groups. The main resistant microorganisms were Enterobacter aerogenes, methicillin resistant Staphylococcus aureus (MRSA), and Enterobacter cloacae. The main susceptible microorganisms were Enterobacter spp., methicillin susceptible S. aureus (MSSA), and Proteus mirabilis. Patients infected with resistant strains had a longer length of stay prior to infection (9+/-4 vs. 5+/-3 days), longer total length of stay (18+/-16 vs. 11+/-7 days), longer duration of mechanical ventilation (12+/-15 vs. 6+/-7 days), and more severe coagulation, liver, and renal dysfunction (all p<0.05). The maximum degrees of organ failure during the ICU stay, and the respiratory dysfunction, but not infection with a resistant pathogen, were independent predictors for death. Multivariate logistic regression revealed previous use of multiple antibiotics, duration of length of stay prior to infection, and the degree of liver failure as independent factors for development of infection with resistant organisms. CONCLUSIONS Infection with antimicrobial resistant microorganisms is not an independent predictor for death. The development of antimicrobial resistance is related to the previous use of multiple antibiotics, the ICU length of stay, and the severity of hepatic dysfunction.

Optimal adrenergic support in septic shock due to peritonitis.

Background The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock. Methods Twenty-eight mature, female, anesthetized sheep (weight, 30.5 ± 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringers solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5–5 &mgr;g · kg−1 · min−1) was titrated to maintain mean arterial pressure between 75–85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 &mgr;g · kg−1 · min−1 dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 &mgr;g · kg−1 · min−1 to get a 15% increase in cardiac output. Results The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do2), and oxygen consumption (&OV0312;o2); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco2) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 ± 4 h), dopamine- norepinephrine (24 ± 6 h), and norepinephrine (20 ± 1 h) groups than the control group (17 ± 2 h;P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 ± 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups. Conclusions In this prolonged septic shock model, association of norepinephrine with either dopamine or dobutamine resulted in the longest survival and the least severe pulmonary lesions. The combination of dobutamine with norepinephrine was associated with a better myocardial performance, greater Do2 and &OV0312;o2, lower blood lactate concentration and Pco2 gap, and less anatomic injury.

Blood Warming during Hemofiltration Can Improve Hemodynamics and Outcome in Ovine Septic Shock

Background:This study was designed to evaluate the effects of blood warming during hemofiltration on global and regional hemodynamics, plasma lactate, and 24-h survival during septic shock. Methods:Twenty anesthetized and mechanically ventilated sheep underwent induction of peritonitis and, 4 h later, were treated by hemofiltration with (n = 10) or without (n = 10) blood warming. Results:In the group without blood warming, body temperature decreased after starting hemofiltration and remained below baseline. In the other animals, body temperature stabilized at baseline level during hemofiltration and increased to a maximum of 40.8°C thereafter. The group without warming experienced a decrease in blood pressure (from 90 mmHg to 38 mmHg) and cardiac output (from 4.0 l/min to 2.3 l/min). Metabolic acidosis and the increase in lactate were less marked when temperature was maintained. None of the animals without warming but all of the animals with warming survived to 16 h. Conclusions:Differences in temperature during hemofiltration resulted in striking differences in hemodynamics, metabolic acidosis, and survival rate in this clinically relevant experimental model of septic shock.