José M. Nicolás

Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial

BACKGROUND Risk factors for nosocomial pneumonia, such as gastro-oesophageal reflux and subsequent aspiration, can be reduced by semirecumbent body position in intensive-care patients. The objective of this study was to assess whether the incidence of nosocomial pneumonia can also be reduced by this measure. METHODS This trial was stopped after the planned interim analysis. 86 intubated and mechanically ventilated patients of one medical and one respiratory intensive-care unit at a tertiary-care university hospital were randomly assigned to semirecumbent (n=39) or supine (n=47) body position. The frequency of clinically suspected and microbiologically confirmed nosocomial pneumonia (clinical plus quantitative bacteriological criteria) was assessed in both groups. Body position was analysed together with known risk factors for nosocomial pneumonia. FINDINGS The frequency of clinically suspected nosocomial pneumonia was lower in the semirecumbent group than in the supine group (three of 39 [8%] vs 16 of 47 [34%]; 95% CI for difference 10.0-42.0, p=0.003). This was also true for microbiologically confirmed pneumonia (semirecumbent 2/39 [5%] vs supine 11/47 [23%]; 4.2-31.8, p=0.018). Supine body position (odds ratio 6.8 [1.7-26.7], p=0.006) and enteral nutrition (5.7 [1.5-22.8], p=0.013) were independent risk factors for nosocomial pneumonia and the frequency was highest for patients receiving enteral nutrition in the supine body position (14/28, 50%). Mechanical ventilation for 7 days or more (10.9 [3.0-40.4], p=0.001) and a Glasgow coma scale score of less than 9 were additional risk factors. INTERPRETATION The semirecumbent body position reduces frequency and risk of nosocomial pneumonia, especially in patients who receive enteral nutrition. The risk of nosocomial pneumonia is increased by long-duration mechanical ventilation and decreased consciousness.

Características clínicas y pronóstico de los pacientes con fibrosis pulmonar que ingresan en cuidados intensivos por insuficiencia respiratoria. Análisis de 20 casos

Fundamento y objetivo: Diversos estudios indican que el pronostico global de los pacientes con fibrosis pulmonar que ingresan en unidades de cuidados intensivos (UCI) es muy malo. El objetivo de este trabajo fue investigar la evolucion y el pronostico de los pacientes con fibrosis pulmonar que requieren ingreso en cuidados intensivos por insuficiencia respiratoria aguda. Pacientes y metodo: Estudio observacional retrospectivo de serie de casos. Se evaluo a los pacientes con fibrosis pulmonar ingresados en la UCI de un hospital terciario entre enero de 1986 y junio de 2002. Se recogieron datos sobre el diagnostico de base, evolucion clinica y tratamiento, estudio funcional respiratorio, ingreso actual, abordaje clinico, ventilacion mecanica, comportamiento mecanico y gasometrico, dias de estancia y mortalidad. Resultados: Se incluyo a 20 pacientes, 14 con fibrosis pulmonar idiopatica y 6 con fibrosis asociada a colagenosis. El tiempo medio (DE) transcurrido desde el diagnostico de fibrosis hasta el ingreso en la UCI fue de 14 (20) meses. Todos presentaban insuficiencia respiratoria grave (PaO2/FiO2 < 200). La causa de la insuficiencia respiratoria se identifico en 8 casos (en 5 era una infeccion bacteriana y en 3 una infeccion fungica). En los 12 casos restantes (60%) no se identifico ningun agente causal. Durante el ingreso en la UCI 17 pacientes precisaron ventilacion mecanica; en los tres casos restantes se limito el esfuerzo terapeutico. Todos, sin excepcion, presentaron una mala evolucion, destacando la alta incidencia de hipoxemia refractaria (100%) e inestabilidad hemodinamica grave tras la intubacion (70%). Tanto la mortalidad asociada a la ventilacion mecanica como la mortalidad intrahospitalaria fueron del 100%. Conclusion: El desencadenante de la insuficiencia respiratoria y el deterioro clinico no son identificables en una proporcion significativa de pacientes a pesar de una aproximacion diagnostica sistematica. La ventilacion mecanica y las medidas de soporte vital agresivo no parecen ofrecer ningun beneficio a los pacientes con fibrosis pulmonar que ingresan en UCI por insuficiencia respiratoria.

Clinical and autopsy correlation evaluated in a University Hospital in Spain (1991-2000)

The authors present a 10-year retrospective study (1991-2000) of all autopsies performed at the Hospital Clinic, Barcelona (Catalonia, Spain) studied by a multidisciplinary committee. The clinicopathologic correlation of the primary underlying disease with the immediate cause of death was reviewed. Between 1991 and 2000, 2,495 autopsies were performed, 1933 of which were evaluated by the committee. The autopsy rate fell from 20% in 1993 to 9.1% in 2000. The clinicopathologic correlation in underlying primary disease was correct in 92.67% of the cases; there was a major discrepancy in 3.51% and a minor discrepancy in 3.82%. As regards the immediate cause of death, major errors were found in 5.89% of cases and minor errors in 6.17%. Despite the scientific and technologic advances in medicine, we have seen that there are still clinicopathologic discrepancies. The postmortem examination continues to play an important role in auditing clinical practice and diagnostic performance, and also for educational purposes. Evaluation by a multidisciplinary committee is the more reliable system for the study of the clinicopathologic correlation.

Effects of Alcohol Withdrawal on 24 Hour Ambulatory Blood Pressure Among Alcohol-Dependent Patients

BACKGROUND Although epidemiologic studies have reported an association between alcohol intake and high blood pressure (BP), the results of intervention studies have shown inconsistent results. We embarked on a study to determine whether different subgroups of alcohol-dependent patients may be identified in relation to the effect of alcohol on BP. METHODS Fifty alcohol-dependent men (mean age, 41.4 years) received 0.4 g of ethanol per kilogram of body weight every 4 hr in 200 ml of orange juice during 24 hr and the same amount of orange juice without ethanol during another 24 hr. Twenty-four hour ambulatory BP monitoring was performed during ethanol and orange juice intakes, as was hormonal and biochemical analysis. RESULTS Thirty-five (75%) alcohol-dependent men were normotensive and 15 (30%) hypertensive. Eighteen (51%) normotensive and 12 (80%) hypertensive subjects showed a significant decrease in 24 hr mean BP after ethanol withdrawal (mean decrease of 8.4 mm Hg [95% confidence interval, -11.2 to -5.7] and 12.5 mm Hg [confidence interval, -16.2 to -8.8], respectively) and were considered as sensitive to alcohol. The remaining alcohol-dependent subjects were considered as resistant to alcohol. Normotensive subjects sensitive to ethanol showed a significantly greater left ventricular mass and a significantly lower ejection fraction than those normotensive patients whose BP did not change after ethanol withdrawal (both p < 0.01). CONCLUSIONS More than three fourths of the hypertensive and more than half of the normotensive alcohol-dependent patients showed sensitivity to the pressor effects of ethanol. Impairment also was observed in heart function in normotensive patients sensitive to the pressor effects of ethanol.

In vivo evolution of resistance of Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit: mechanisms of resistance and antimicrobial exposure

OBJECTIVES The main objective of this study was to investigate the relationship among the in vivo acquisition of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates, the underlying molecular mechanisms and previous exposure to antipseudomonal agents. METHODS PFGE was used to study the molecular relatedness of the strains. The MICs of ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin and amikacin were determined. Outer membrane protein profiles were assessed to study OprD expression. RT-PCR was performed to analyse ampC, mexB, mexD, mexF and mexY expression. The presence of mutations was analysed through DNA sequencing. RESULTS We collected 17 clonally related paired isolates [including first positive samples (A) and those with MICs increased ≥4-fold (B)]. Most B isolates with increased MICs of imipenem, meropenem and ceftazidime became resistant to these drugs. The most prevalent resistance mechanisms detected were OprD loss (65%), mexB overexpression (53%), ampC derepression (29%), quinolone target gene mutations (24%) and increased mexY expression (24%). Five (29%) B isolates developed multidrug resistance. Meropenem was the most frequently (71%) received treatment, explaining the high prevalence of oprD mutations and likely mexB overexpression. Previous exposure to ceftazidime showed a higher impact on selection of increased MICs than previous exposure to piperacillin/tazobactam. CONCLUSIONS Stepwise acquisition of resistance has a critical impact on the resistance phenotypes of P. aeruginosa, leading to a complex scenario for finding effective antimicrobial regimens. In the clinical setting, meropenem seems to be the most frequent driver of multidrug resistance development, while piperacillin/tazobactam, in contrast to ceftazidime, seems to be the β-lactam least associated with the selection of resistance mechanisms.

El anciano en la unidad de cuidados intensivos

Admission of elderly patients to intensive care units (ICU) is an increasing phenomenon. The severity of the disease causing admission and the basal functional patients status are conditions more important than age to predict mortality and long term functional outcome. Studies demonstrate that elderly ICU survivors recover after discharge the majority part of their functional capability and perception of quality of life. On the contrary, these patients develop higher number of geriatric syndromes, mainly confusional syndrome. The culture of geriatric comprehensive assessment should be implemented in ICU and especially after discharge. The use of simple and validates scales (Barthels Index, Lawtons Index and EuroQol-5D...) must be incorporated into the clinical practice. This is a good tool that could be useful for the specialists involved in the usually difficult decision of whether an elderly patient should or not be admitted to an ICU.

Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes

Objective To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes. Methods Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters. Results A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5–1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6–1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5–1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7–1.3). Conclusions A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality.

Effects of different antigenic stimuli on thymic function and interleukin-7/CD127 system in patients with chronic HIV infection.

Background:We tested if an increase in immune activation and a decrease in CD4+ T cells induced by different antigenic stimuli could be associated with changes in the thymic function and the interleukin (IL)-7/CD127 system. Methods:Twenty-six HIV-infected patients under combined antiretroviral therapy (cART) were randomized to receive, during 12 months, a complete immunization schedule (7 vaccines and 15 doses) or placebo. Thereafter, cART was interrupted during 6 months. Changes in the thymic function and the IL-7/CD127 system after 3 different antigenic stimuli (vaccines, episodes of low-level intermittent viremia before cART interruption, or viral load rebound after cART interruption) were assessed. Results:During the period on cART, neither vaccines nor low-level viremia influenced thymic function or IL-7/CD127 system parameters. By analyzing the cohort as a whole while on cART, a significant improvement was observed in the thymic function as measured by an increase in the thymic volume (P = 0.024), T-cell receptor excision circle–bearing cells (P = 0.012), and naive CD4+ and CD8+ T cells (P = 0.069 both). No significant changes were observed in the IL-7/CD127 system. After cART interruption, a decrease in T-cell receptor excision circles (P < 0.001) and naive CD8+ T cells (P < 0.001), an increase in IL-7 and expression of CD127 on naive and memory CD4+ T cells (P = 0.028, P = 0.088, and P = 0.04, respectively), and a significant decrease in CD127 on naive and memory CD8+ T cells (P = 0.01, P = 0.006, respectively) were observed. Conclusions:Low-level transient antigenic stimuli during cART were not associated with changes in the thymic function or the IL-7/CD127 system. Conversely, viral load rebound very early after cART interruption influenced the thymic function and the IL-7/CD127 system. Clinical Trials.gov number NCT00329251.

Acute iron intoxication: change in urine color during chelation therapy with deferoxamine

A 21-year-old woman presented to the emergency department 8 h after the ingestion of 5,100 mg of ferrous sulfate (110 mg/kg) in a suicide attempt. At admission she was hemodynamically stable without pathologic findings at examination. Laboratory tests showed a mild decrease in prothrombin time and a compensated metabolic acidosis with normal renal function and liver enzymes. An abdominal x-ray showed normal findings without visible radiopaque pills. Initial serum iron levels were 300 lg/dL. The patient was transferred to the intensive care unit for monitoring. Chelation therapy with deferoxamine was then started at 15 mg/kg/24 h and the patient’s urine turned a red– orange color after starting this treatment (Fig. 1). After 24 h of treatment serum iron levels decreased to 87 lg/dL and chelation therapy was withdrawn. The patient remained clinically stable with no medical complications. She was discharged from hospital 5 days after admission. Deferoxamine is a specific iron chelator that binds ferric iron forming a water-soluble compound that is rapidly excreted by the kidney, causing a vin rosé discoloration to the urine. It is considered the drug of choice for the treatment of significant iron intoxication. Change in urine color may confirm the effectiveness of this antidote.

Infecciones relacionadas con el uso de catéteres venosos centrales y sistemas organizativos de las unidades de cuidados intensivos (estudio EPIC)

Fundamento y objetivo: La bacteriemia nosocomial relacionada con el empleo de cateteres venosos centrales (CVC) es un problema importante en las unidades de cuidados intensivos (UCI). El papel que desempenan el sistema organizativo y la experiencia de los profesionales sanitarios en este proceso es poco conocido. El objetivo de este estudio fue identificar posibles relaciones y diferencias entre los procesos asistenciales, la organizacion de las UCI y el desarrollo de bacteriemia nosocomial relacionada con el uso de CVC y analizar los resultados de un hospital espanol junto a los registrados en un grupo internacional de hospitales. Pacientes y metodo: El estudio EPIC (Evaluation of Processes and Indicators in Infection Control) incluyo hospitales de distintos paises. El Hospital Clinic de Barcelona fue el unico participante espanol. Cada centro selecciono, mediante un muestreo aleatorio, a 5 pacientes por mes, ingresados en una misma UCI, a los que se habia colocado recientemente (en un intervalo inferior a 24 h) un CVC. Se obtuvieron datos relativos al proceso de insercion del CVC, su seguimiento y sus cuidados, dedicacion del personal de enfermeria, numero de dias de estancia en UCI y episodios de bacteriemia nosocomial por 1.000 dias de uso de CVC. Resultados: Se incluyo a un total de 3.298 pacientes portadores de CVC, en los que se registraron 89 episodios de bacteriemia nosocomial (3,86 episodios por 1.000 dias de uso de cateter). El Hospital Clinic incluyo a 67 pacientes, en los que se registraron 1,96 episodios de bacteriemia nosocomial por 1.000 dias de uso de CVC. El centro espanol empleaba con mas frecuencia gasa esteril y cinta adhesiva para la fijacion del CVC que el grupo internacional de 55 hospitales (70 frente al 23%), cada profesional sanitario espanol colocaba menos CVC en promedio en los 6 meses precedentes que sus colegas internacionales (24 frente a 50) y los CVC eran colocados en el Hospital Clinic con mayor frecuencia por personal de enfermeria (48 frente al 4%). El tipo de CVC mas empleado en el Hospital Clinic era el de insercion periferica (48 frente al 6%), y era retirado antes del alta del paciente de la UCI en menos ocasiones (16 frente al 43%). La media de horas totales de dedicacion de personal de enfermeria era mas baja en Espana, con indices de personal (numero de horas de enfermeria) por dia de estancia del paciente tambien inferiores a los internacionales (12 frente a 15). Conclusiones: El estudio EPIC proporciona un conjunto de instrumentos validos para evaluar el proceso asistencial y relacionar este proceso con sus resultados. Los resultados finales observados en el hospital espanol son adecuados, y se observan diferencias notables en el proceso asistencial.