Impact of antibiotics on the gut microbiota of critically ill patients.

We evaluated the relationship between the intestinal microbiota composition and clinical outcome in a group of 15 high-risk patients admitted for acute infection and/or surgical/accidental trauma who were treated with systemic antibiotics according to standard intensive care unit (ICU) protocols. There was a high mortality rate amongst these patients, each of whom had a considerable organ failure score at admission, respiratory assistance during the most of their ICU stay and a long length of stay. All of these individuals received sedation and enteral nutrition, and the majority also received insulin, vasoactive drugs and some stress-ulcer prophylaxis agents. The intestinal microbiota composition was assessed using denaturing gradient gel electrophoresis (DGGE), a molecular biology tool used to characterize bacterial ecosystems. As all of the patient subjects were in good health prior to their acute illness and admission to the ICU, the first faecal samples obtained from this group showed a DGGE banding pattern that was similar to that of healthy subjects. After 1 week of critical illness, coupled with intensive care treatment, including antibiotics, a very definite alteration in the overall microbiota composition was evident, as revealed by a reduction in the number of DGGE bands. Further pronounced changes to the DGGE banding profiles could be observed in patients remaining in the ICU for 2 weeks. Moreover, a dominant band, identified by sequencing as highly related to Enterococcus, was detected in the DGGE profile of some of our patient subjects. We also performed real-time PCR and obtained results that were in agreement with our qualitative evaluations using DGGE. The degree of organ failure and ICU mortality was significantly higher in patients for whom a high reduction in microbiota biodiversity was coupled with a massive presence of enterococci. A statistically significant link between these two ecological traits and the use of clindamycin was also found.

Neurological assessment with validated tools in general ICU: multicenter, randomized, before and after, pragmatic study to evaluate the effectiveness of an e-learning platform for continuous medical education.

BACKGROUND: International guidelines recommend systematic assessment of pain, agitation/sedation and delirium with validated scales for all ICU patients. However, these evaluations are often not done. We have created an e-learning training platform for the continuous medical education, and assessed its efficacy in increasing the use of validated tools by all medical and nursing staff of the participating ICUs during their daily practice. METHODS: Multicenter, randomized, before and after study. The eight participating centers were randomized in two groups, and received training at different times. The use of validated tools (Verbal Numeric Rating or Behavioral Pain Scale for pain; Richmond Agitation-Sedation Scale for agitation; Confusion Assessment Method for the ICU for delirium) was evaluated from clinical data recorded in medical charts during a week, with follow-up up to six months after the training. All the operators were invited to complete a questionnaire, at baseline and after the training. RESULTS: Among the 374 nurses and physicians involved, 140 (37.4%) completed at least one of the three courses. The assessment of pain (38.1 vs. 92.9%, P<0.01) and delirium (0 vs. 78.6%, P<0.01) using validated tools significantly increased after training. Observation in the follow-up showed further improvement in delirium monitoring, with no signs of extinction for pain and sedation/agitation measurements. CONCLUSIONS: This e-learning program shows encouraging effectiveness, and the increase in the use of validated tools for neurological monitoring in critically ill patients lasts over time.

Sedation in the critically ill ventilated patient: possible role of enteral drugs.

OBJECTIVE: Sedation by the enteral route is unusual in intensive medicine. We analysed the feasibility/efficacy of long-term enteral sedation in ventilated critically ill patients. DESIGN: Prospective interventional cohort study. SETTING: General ICU. PATIENTS AND PARTICIPANTS: Forty-two patients needing ventilation and sedation for at least 4 days. INTERVENTIONS: At admission, sedation was induced with propofol or midazolam. Enteral hydroxyzine (+/- enteral lorazepam) was added in all patients within the second day. Intravenous drugs were gradually withdrawn, trying to maintain only enteral sedation after the initial 48 h. Analgesia was provided with continuous IV fentanyl. MEASUREMENTS AND RESULTS: Sedation level was assessed evaluating, on a daily basis, patients' compliance to the invasive care and comparing observed vs planned Ramsay scores three times a day. Excluding the first 2 days of patient-stabilisation and fast titration of sedation level, 577 days with ventilatory support were analysed. In 460 days (79.7%) total enteral sedation was given. This percentage rose to 94.2% when the requested Ramsay was 2 (347 days). Daily sedation was judged as adequate in 82.8% of days of total enteral sedation. Thirty-one patients had total enteral as the exclusive route of sedation. CONCLUSIONS: After 24-48 h, enteral sedation may replace, totally/in part, IV sedation in ventilated patients. Total enteral sedation easily fits the target when a Ramsay score 2 is planned. When a deeper sedation is needed, a mixed regimen is effective and lowers IV drug dosages. No side effects were reported.

Short-term noninvasive pressure support ventilation prevents ICU admittance in patients with acute cardiogenic pulmonary edema.

STUDY OBJECTIVES: Noninvasive ventilation, although effective as treatment for patients with acute cardiogenic pulmonary edema when prolonged for hours, is of limited use in the emergency department (ED). The aim of the study was to determine whether a short attempt at noninvasive pressure support ventilation avoids ICU admittance and to identify lack of response prediction variables. DESIGN: Prospective inception cohort study. SETTING: ED of a university hospital. PATIENTS: Fifty-eight consecutive patients with cardiogenic pulmonary edema who had been unresponsive to medical treatment and were admitted between January 1999 and December 2000. INTERVENTIONS: Pressure support ventilation was instituted through a full-face mask until the resolution of respiratory failure. A 15-min "weaning test" was performed to evaluate clinical stability. Responder patients were transferred to a medical ward. Nonresponding patients were intubated and were admitted to the ICU. MAIN OUTCOME MEASURES: The included optimal length of intervention, the avoidance of ICU admittance, the incidence of myocardial infarction, and predictive lack of response criteria. RESULTS: Patients completed the trial (mean [+/- SD] duration, 96 +/- 40 min). None of the responders (43 patients; 74%) was subsequently ventilated or was admitted to the ICU. Two new episodes of myocardial infarction were observed. Thirteen of 58 patients died. A mean arterial pressure of < 95 mm Hg (odds ratio [OR], 10.6; 95% confidence interval [CI], 1.8 to 60.8; p < 0.01) and COPD (OR, 9.4; 95% CI, 1.6 to 54.0; p < 0.05) at baseline predicted the lack of response to noninvasive ventilation. CONCLUSIONS: A short attempt at noninvasive ventilation is effective in preventing invasive assistance. A 15-min weaning test can identify patients who will not need further invasive ventilatory support. COPD and hypotension at baseline are negative predictive criteria.

Bias reduction in repeated-measures observational studies by the use of propensity score: the case of enteral sedation for critically ill patients.

PURPOSE: Within the evidence-based medicine paradigm, randomized controlled trials represent the "gold standard" to produce reliable evidence. Indeed, planning and implementing randomized controlled trials in critical care medicine presents limitations because of intrinsic and structural problems. As a consequence, observational studies still occur frequently. In these cases, propensity score (PS) (probability of receiving a treatment conditional on observed covariates) is an increasingly used technique to adjust the results. Few studies addressed the specific issue of a PS correction of repeated-measures designs. MATERIALS AND METHODS: Three techniques for correcting the analysis of nonrandomized designs (matching, stratification, regression adjustment) are presented in a tutorial form and applied to a real case study: the comparison between intravenous and enteral sedative therapy in the intensive care unit setting. RESULTS: After showing the results before and after the use of PS, we suggest that such a tool allows to partially overcoming the bias associated with the observational nature of the study. It permits to correct the estimates for any observed covariate, while unobserved confounders cannot be controlled for. CONCLUSIONS: Propensity score represents a useful additional tool to estimate the effects of treatments in nonrandomized studies. In the case study, an enteral sedation approach was equally effective to an intravenous regime, allowing for a lower level of sedation and spare of resources.

Actigraphic monitoring in critically ill patients: preliminary results toward an "observation-guided sedation".

PURPOSE: The aim of this study is to evaluate continuous wrist actigraphy (measurement of limb movements) in intensive care unit patients as a neurologic status monitoring. MATERIALS AND METHODS: This is a prospective, observational study on motor activity of adult patients using wrist actigraphs. Nurses recorded the number of sleep and agitation hours as well as assessed pain and anxiety level (verbal numeric rating) and the agitation/sedation level (Richmond Agitation-Sedation Scale). RESULTS: Thirteen mechanically ventilated patients were studied during their whole intensive care unit stay (total, 165 patients/d). The number of surveyed movements was gathered for each hour, obtaining an estimation of patient motor status. This measure was different between days and nights (33.3 [20.3-49.0] vs 8.5 [4.4-13.8]; P < .001), with a correlation with sleeping hours estimated by nurses (P = .017 during the days [D], P < .001 during the nights [N]), agitation hours (P = .002 D, P = .017 N), Richmond Agitation-Sedation Scale value (P < .001 D and N), pain (P = .012 D), and anxiety (P < .001 D) verbal numeric rating. No differences were found using epochs of 15 or 120 seconds. Compliance with patients and nurses was acceptable. CONCLUSIONS: Patients' limb movements were significantly related to all studied neurologic status indexes. Continuous actigraphy measuring may become important as a clinical tool both to guide utilization of sedative drugs and to enhance early recognition and management of agitation.

Conscious sedation in the critically ill ventilated patient.

PURPOSE: The aim of sedation is to provide comfort and minimize anxiety. However, adverse effects are noteworthy, and the optimal end point of sedation in intensive care unit patients is still debated. We analyzed if a level 2 on the Ramsay Scale (ie, awake, cooperative, oriented, tranquil patient) is suitable for an invasive therapeutic approach. MATERIALS AND METHODS: Forty-two patients requiring respiratory support and sedation for at least 4 days were enrolled in a prospective interventional cohort study aiming at maintaining patients awake and collaborative. The Ramsay score was recorded 3 times a day. Once a day, the nurse in charge evaluated adequacy of sedation according to the compliance with nursing care and therapeutic maneuvers in the previous 24 hours. Data were collected until patients were ventilated. RESULTS: Overall, 264 of 582 days were classified as conscious. Sedation was adequate in 93.9% of them. In conscious days, a higher Simplified Acute Physiology Score II score and male sex significantly correlated with inadequate sedation. CONCLUSIONS: In a population of severe intensive care unit patients, conscious sedation was achieved in almost half of the days spent on ventilation. The positive implications (eg, on length of weaning and cost of sedation) of a conservative sedation strategy may be highly relevant.