Aggressive versus conservative antibiotic use to prevent and treat ventilator-associated pneumonia in patients with severe traumatic brain injury: comparison of two case series.

BACKGROUND: In patients with traumatic brain injury (TBI), ventilator-associated pneumonia (VAP) is considered a dangerous complication, prompting early aggressive antibiotic treatment and prophylaxis. While this approach increases the selection of multidrug-resistant bacteria (MDR), its clinical benefit has not been demonstrated. METHODS: One-year incidence of VAP in severe TBI patients (ICU stay >48 hours, with either Glasgow Coma Scale ≤8 or receiving intracranial pressure monitoring, or having undergone emergency surgery) and the prevalence of MDR among those who eventually developed it, were compared in two Italian intensive care units (ICUs) adopting different antibiotic approaches. Antibiotic use was guideline-driven and aggressive in the Pisa-based unit (165 eligible patients), and very conservative and coupled with non-pharmacological prevention measures in Cesena (262 patients). Data were also compared with those of 208 Italian ICUs participating in the same infection surveillance program. RESULTS: Patient case mix and general care were similar in the two units. Overall antibiotic pressure was higher in Pisa (58.9% vs. 26.1% of beds occupied by patients receiving antibiotics, P<0.0001), as was antibiotic prophylaxis in eligible patients (87.3% vs. 7.6%, P<0.0001; Italian ICUs, 69.2%) and empirical therapy in those who developed VAP (60.8% vs. 25.2%, P<0.0001; Italian ICUs, 51.6%). The incidence rate of VAP did not significantly differ (39.8 per 1000 days of mechanical ventilation in Pisa, 49.3 in Cesena, P=0.16), although it occurred earlier in Cesena (23.0% early VAP in Pisa vs. 61.2% in Cesena, P<0.0001). Mortality was higher in Pisa but Cesena transferred more patients to other hospitals, precluding comparison of the two rates. The prevalence of MDR was higher in Pisa (38.2% vs. 9.9%, P<0.0001; Italian ICUs, 30.2%). CONCLUSIONS: Although not conclusive, these results call into question the prevalent aggressive use of antibiotics in TBI patients and urge the scientific community to produce better evidence for clinical recommendations.

Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study.

INTRODUCTION: Critical illness myopathy and/or neuropathy (CRIMYNE) is frequent in intensive care unit (ICU) patients. Although complete electrophysiological tests of peripheral nerves and muscles are essential to diagnose it, they are time-consuming, precluding extensive use in daily ICU practice. We evaluated whether a simplified electrophysiological investigation of only two nerves could be used as an alternative to complete electrophysiological tests. METHODS: In this prospective, multi-centre study, 92 ICU patients were subjected to unilateral daily measurements of the action potential amplitude of the sural and peroneal nerves (compound muscle action potential [CMAP]). After the first ten days, complete electrophysiological investigations were carried out weekly until ICU discharge or death. At hospital discharge, complete neurological and electrophysiological investigations were performed. RESULTS: Electrophysiological signs of CRIMYNE occurred in 28 patients (30.4%, 95% confidence interval [CI] 21.9% to 40.4%). A unilateral peroneal CMAP reduction of more than two standard deviations of normal value showed the best combination of sensitivity (100%) and specificity (67%) in diagnosing CRIMYNE. All patients developed the electrophysiological signs of CRIMYNE within 13 days of ICU admission. Median time from ICU admission to CRIMYNE was six days (95% CI five to nine days). In 10 patients, the amplitude of the nerve action potential dropped progressively over a median of 3.0 days, and in 18 patients it dropped abruptly within 24 hours. Multi-organ failure occurred in 21 patients (22.8%, 95% CI 15.4% to 32.4%) and was strongly associated with CRIMYNE (odds ratio 4.58, 95% CI 1.64 to 12.81). Six patients with CRIMYNE died: three in the ICU and three after ICU discharge. Hospital mortality was similar in patients with and without CRIMYNE (21.4% and 17.2%; p = 0.771). At ICU discharge, electrophysiological signs of CRIMYNE persisted in 18 (64.3%) of 28 patients. At hospital discharge, diagnoses in the 15 survivors were critical illness myopathy (CIM) in six cases, critical illness polyneuropathy (CIP) in four, combined CIP and CIM in three, and undetermined in two. CONCLUSION: A peroneal CMAP reduction below two standard deviations of normal value accurately identifies patients with CRIMYNE. These should have full neurological and neurophysiological evaluations before discharge from the acute hospital.

Variable costs of ICU patients: a multicenter prospective study.

OBJECTIVE: To analyze the costs of treating critically ill patients. DESIGN AND SETTING: Multicenter, observational, prospective, cohort, bottom-up study on variable costs in 51 ICUs. PATIENTS AND PARTICIPANTS: A total of 1,034 patients aged over 14 years who either spent less than 48 h in the ICU or had multiple trauma, major abdominal surgery, ischemic stroke, chronic obstructive pulmonary disease, cardiac failure, isolated head injury, acute lung injury/adult respiratory distress syndrome (ALI/ARDS), nontraumatic intracranial hemorrhage or coronary surgery. INTERVENTIONS: Data recorded for each patient: length of ICU stay, and cost in euros of all diagnostic and therapeutic procedures, drugs and equipment used, and consultations by physicians from other units. To express cost-efficiency we calculated for each diagnostic group the cost per surviving patient (expenditure for all patients/number of surviving patients) and money loss per patient (expenditure for patients who died/total number of patients). MEASUREMENTS AND RESULTS: Median costs for a multiple trauma patient were euro 4076 and for coronary surgery patient euro 380. The variability is largely due to different lengths of ICU stay. Cost per surviving patient was higher for ALI/ARDS, nontraumatic intracranial hemorrhage, multiple trauma, and emergency abdominal surgery. Money loss per patient was higher for ALI/ARDS and lower for multiple trauma. Planned coronary and major abdominal surgery and short-stay patients were treated most cost-efficiently. CONCLUSIONS: Cost of treatment in an ICU varies widely for different types of patients. Strategies are needed to contain the major determinants of high costs and low cost-efficiency.

Costs of the COPD. Differences between intensive care unit and respiratory intermediate care unit.

INTRODUCTION: To assess whether respiratory intermediate care units (RICUs) are cost effective alternatives to intensive care units (ICUs) for patients with exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Multi-centre, prospective, bottom-up cost study performed in 15 ICUs and 6 RICUs. COPD patients staying longer than 48 h were recruited; those coming from other ICUs/RICUs, with immune-deficiency or stroke, were excluded. After the ICU sample was standardised to the RICU distribution of the reason-for-admission and infusion of a vasoactive drug on admission, 60 ICU patients and 65 RICU patients remained, of the original 164 recruited. For each patient, besides clinical data on admission and discharge, daily information about the resources consumed were recorded and analysed in terms of their costs. RESULTS: Total cost per patient was lower in RICUs than in ICUs (754 vs. 1507 Euro; P < 0.0001). In all items, except drugs and nutrition, we found a significant lower cost in RICUs. Dead patients were noticeably different in terms of disease severity between ICUs and RICUs, while surviving ones were not. CONCLUSIONS: Our study suggests that some COPD patients, less severe and with pure respiratory failure, could be successfully and less costly treated in RICUs.

Volume of activity and occupancy rate in intensive care units. Association with mortality.

OBJECTIVE: Mortality after many procedures is lower in centers where more procedures are done. It is controversial whether this is true for intensive care units, too. We examined the relationship between the volume of activity of intensive care units (ICUs) and mortality by a measure of risk-adjusted volume of activity specific for ICUs. DESIGN: Prospective, multicenter, observational study. SETTING: Eighty-nine ICUs in 12 European countries. PATIENTS: During a 4-month study period, 12,615 patients were enrolled. INTERVENTIONS: Demographic and clinical statistics, severity at admission and a score of nursing complexity and workload were collected. RESULTS: Total volume of activity was defined as the number of patients admitted per bed per year, high-risk volume as the number of high-risk patients admitted per bed per year (selected combining of length of stay and severity of illness). A multi-step risk-adjustment process was planned. ICU volume corresponding both to overall [odds ratio (OR) 0.966] and 3,838 high-risk (OR 0.830) patients was negatively correlated with mortality. Relative mortality decreased by 3.4 and 17.0% for every five extra patients treated per bed per year in overall volume and high-risk volume, respectively. A direct relationship was found between mortality and the ICU occupancy rate (OR 1.324 and 1.351, respectively). CONCLUSIONS: Intensive care patients, whatever their level of risk, are best treated where more high-risk patients are treated. Moreover, the higher the ICU occupancy rate, the higher is the mortality.

The relationship between labour cost per patient and the size of intensive care units: a multicentre prospective study.

OBJECTIVE: We examined the relationship between major ICU characteristics and labour cost per patient. DESIGN: Four-week prospective data collection, in which the hours spent by each physician and nurse on both in-ICU and extra-ICU activities were collected. SETTING: Eighty Italian adult ICUs. MEASUREMENTS AND RESULTS: The cost of the time actually spent by ICU staff on ICU patients (labour cost) was computed for each participating unit, by applying to the average annual salaries the proportions of in-ICU activity working time for physicians and nurses. Multiple regression analysis was used to identify ICU characteristics that predict labour costs per patient. Labour cost per patient was positively correlated with ICU mortality and patients average length of stay (slopes =0.67, p =0.048 and 0.09, p <0.0001, respectively). Labour cost per patient decreases almost linearly as the number of beds increases up to about eight, and it remains nearly constant above about twelve beds. The number of patients admitted per physician (not per nurse) increases with the number of beds (Spearman correlation coefficient =0.567, p <0.0001). CONCLUSIONS: Our findings suggest that ICUs with less than about 12 beds are not cost-effective.

Early enteral immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized multicentre clinical trial.

OBJECTIVE: To compare the mortality of critically ill patients given either enteral feeding with an immune-enhancing formula or parenteral nutrition (PN). We report the results of a planned interim analysis on patients with severe sepsis which was undertaken earlier than planned once a meta-analysis suggested excess mortality in patients with severe sepsis given enteral immunonutrition. DESIGN: Randomised multicentre unblinded controlled clinical trial. SETTING: Thirty-three General Intensive Care Units in Italy. PATIENTS AND PARTICIPANTS: Among the 237 recruited patients, 39 had severe sepsis or septic shock; 21 of them received PN. INTERVENTIONS: Eligible patients received either total PN or enteral nutrition, the latter containing extra L-arginine, omega-3 fatty acids, vitamin E, beta carotene, zinc, and selenium. MEASUREMENTS AND RESULTS: The primary endpoint for the subgroup analysis on patients with severe sepsis was mortality on Intensive Care Unit (ICU). The ICU mortality of patients with severe sepsis given enteral nutrition (EN) was higher than for those given PN (44.4% vs 14.3%; p=0.039). More patients given EN than patients given PN still had severe sepsis when they died (38.9% vs 9.5%, p=0.055). Recruitment of patients with severe sepsis was subsequently stopped. CONCLUSIONS: Our results show that enteral immunonutrition, compared to PN, may be associated with excess mortality in patients with severe sepsis.