Caspofungin PK in critically ill patients after the first and fourth doses: suggestions for therapeutic drug monitoring?

We describe caspofungin pharmacokinetics (PK) after the first and fourth doses in 20 critically ill septic patients. Monte Carlo simulation was used to analyze the probability of target attainment (PTA) (AUC/MIC > 865) for Candida spp. Caspofungin concentrations were analyzed by HPLC in plasma and urine. A great variability in PK parameters was observed after both doses. Patients were divided in two groups according to their AUC values (AUC ≤ 75 mg h/L cut-off). In the low-AUC group Cmax, Cmin and AUC were lower, while Vd and Cl were higher than in the high-AUC group (p < 0.05, both at day 1 and 4). The mean 24-h urinary recovery of the drug was 8 ± 6.3% (day1) and 9.8 ± 6.3 (day4). Monte Carlo simulation analysis (0.03-1 mg/L MIC-range) showed that PTA was guaranteed only for MICs ≤ 0.03 mg/L in the low-AUC group, and for MICs ≤ 0.06 mg/L in the high-AUC group. No group had a PTA ≥ 90% for 0.125 mg/L MIC (the epidemiological cut-off). Mortality was higher in low-AUC group (p < 0.01). In our 'real-world' population, no clinical data can predict which patient will have lower, suboptimal caspofungin exposure, therefore we suggest TDM to optimize caspofungin therapy and reduce the risk of selecting resistances (CEAVC, 32366/2015; OSS.15.114, NCT03798600).

Implementation and preliminary validation of a new score that predicts post-operative complications.

BACKGROUND: An accurate pre-operative risk assessment could reduce morbidity and mortality for high-risk surgical patients. The aim of the study was to implement and preliminary validate a new score that could predict the occurrence of post-operative complications (PoCs): the Anesthesiological and Surgical Postoperative Risk Assessment (ASPRA) score. METHODS: The ASPRA score was created through a literature's review; a score of 1-3 was given to each identified risk factor, according to its statistical correlation with PoC. ASPRA was retrospectively applied to a derivation set of 176 surgical patients. A receiver operating characteristic (ROC) analysis evaluated the discriminating ability of the score and cutoff value in predicting the occurrence of PoCs, according to the Clavien-Dindo classification of surgical complications. The statistical validation of the score and related cutoff values was prospectively ran within a validation set of 1928 surgical patients. RESULTS: Through ROC analysis, an ASPRA score of 7 was chosen as the cutoff value in the derivation set. In the validation set, 65.3% of patients presented a PoC (Clavien ≥ 1). In this group, ROC analysis showed an area under the curve (AUC) of 0.72, and although potentially related to the high rate of complications a high positive predictive value of 87.0% has been observed. No significant differences were found in ROC-AUC, sensitivity, specificity, or positive or negative predictive value between the derivation and validation sets (P > 0.05). CONCLUSION: The new ASPRA score has a high positive predictive value to predict the occurrence of PoCs. Further prospective studies are required to confirm these results.

Development of END-of-Life ScorING-System to identify critically ill patients after initial critical care who are highly likely to die: a pilot study.

BACKGROUND: High quality palliative care should be provided for the dying patients in the intensive care unit (ICU). The aim of this pilot study is to develop a scoring system, the "END-of-Life ScorING-System" (ENDING-S), that may help to identify ICU patients at very high risk of dying after initial response to the intensive treatments and which could be used to facilitate palliative care. METHODS: The characteristics of longer-term ICU patients (>4 days) who are at very high risk of dying were identified through an analysis of the literature and developed in a retrospective cohort of patients. ENDING-S Score was developed through a multivariate analysis. Model accuracy was tested through ROC and Hosmer-Lemeshow analysis for model discrimination and calibration respectively. Cross validation was used to provide internal model validation. RESULTS: Potential predictors of death were identified and applied to 80 ICU patients. Significant variables in the multivariate analysis were the ratio of the ICU days in which the patient needs mechanical ventilation or vasoactive drugs divided by the total ICU days, the total ICU length of stay, and current sepsis. Analysis of accuracy showed a ROC-AUC equals to 0.98 (95% CI, 0.97 to 1), and agreement between the predicted probability and the observed frequency of death in the ICU was observed (P>0.05 at Hosmer-Lemeshow test). The internal validation confirms these results. CONCLUSION: In these preliminary results, ENDING-s shows acceptable calibration and discrimination properties. ENDING-S may raise awareness among ICU physicians about the importance of integrating palliative care into ICU daily practice.

Use of the parenteral antibiotic Ertapenem as short term prophylaxis in bariatric surgery: a pharmaco-kinetic-pharmacodynamic study in class III obese female patients.

BACKGROUND: The objective of this study was to determine the pharmacokinetics-pharmacodynamics (PK/PD) of Ertapenem in extremely obese female patients (Body Mass Index [BMI] ≥ 40 kg/m²) undergoing bariatric surgery. METHODS: Ten patients received 1 g intravenous Ertapenem 0.5 h prior to surgery as short term prophylaxis. Serum Ertapenem concentrations were determined at baseline, at the end of infusion (30 minutes), then at 1, 2, 4, 8, 12 and 24 hours postinfusion. In patients in whom a liver biopsy was necessitated by clinical need, Ertapenem liver concentrations were determined through intraoperative biopsies at 1 and 2 h postadministration. Peritoneal Ertapenem concentrations were determined in drainage fluid samples collected during the 4-8, 8-12, and 12-24 h intervals after Ertapenem administration. A Monte Carlo simulation was performed to estimate the probability of achieving free drug levels above the minimum inhibitory concentration (fT>MIC) for at least 20% and 40% of the dosing interval as PK/PD targets. RESULTS: Peak drug concentration and 24-h area under the concentration-time curve (AUC) were found to be 191.9 ± 37.4 mg/L and 574.3 ± 110.5 mg·h/L, respectively. Ertapenem liver/serum concentration ratios were 6% at 1 h and 5% at 2 h. Drug concentrations in peritoneal fluid were 28.2 ± 6.4 mg/L at 4-8h, declined to 15.2 ± 5.9 at 8-12h and fell further to 4.79 ± 0.2 mg/L at 12-24 h post-administration. The probability to reach the desired PK/PD targets were never reached at any MICs >0.25 µg/mL with a 90% probability. CONCLUSION: Our data suggest that in extremely obese female patients, the standard dose of 1 g i.v. Ertapenem as short term prophylaxis may not provide optimal clinical levels of free drug for prevention of surgical site infections.

Preoperative medication with oral morphine sulphate and postoperative pain.

BACKGROUND: The administration of an analgesic drug prior to nociceptive surgical stimulus could result in a better postoperative pain management. The aim of this study was to evaluate the effect of preoperative oral morphine sulphate on postoperative pain relief. METHODS: Sixty patients undergoing major abdominal surgery were randomly assigned to premedication with 0.5 mg/kg oral morphine sulphate (oral morphine group) or 0.05 mg/kg oral midazolam (active placebo group). Primary outcome was efficacy of morphine premedication on opioid administration of IntraVenous Patient Controlled Analgesia (IVPCA) doses, at 4, 24, and 48 hours after completion of surgery and reducing static and dynamic visual analogue scale (sVAS and dVAS) scores. Secondary outcome was the time needed for the recovery of canalization of the gastro-intestinal tract. It was also evaluated fentanyl intraoperative consumption. Statistical analysis was performed by linear regression and student t test. Values of P<0.05 were considered significant. RESULTS: The two groups were comparable with respect to patient characteristics. At 24 and 48 hours post surgery, administered IVPCA doses were reduced in the oral morphine group compared to the active placebo group (P<0.05). Values of sVAS and dVAS were significantly lower in the oral morphine group compared to the active placebo group at all assessment times (P<0.05). Fentanyl consumption was similar in both groups. Needs of a ketorolac rescue dose was greater in the ap versus the om group (21 patients in the ap vs 9 patients in the om group, P<0.001). Mean gastrointestinal canalization did not significantly differ between groups. CONCLUSIONS: In major abdominal surgery, premedication with oral morphine sulphate produces better postoperative pain control and has an opioid-sparing effect without delaying gastrointestinal canalization time.

Do we need to use sugammadex at the end of a general anesthesia to reverse the action of neuromuscular bloking agents? Position Paper on Sugammadex use.

Sugammadex, the first selective relaxant-binding agent indicated to reverse the neuromuscular blockade induced during general anesthesia, was recently introduced into clinical practice. In the present report, the following issues pertinent to the use of sugammadex in anesthesia practice are discussed: the intraoperative use of NMBAs and the incidence of postoperative residual curarization (PORC); the efficacy and safety of rocuronium plus sugammadex compared to succinylcholine for rapid sequence induction; the availability of sugammadex in hospitals; and, finally, some relevant legal medical aspects. Sugammadex is considerably more expensive than neostigmine, but its use can be advocated based on its safety and efficacy profile as a reversal agent of steroidal neuro muscular blocking agents (NMBAs), and as a mean to prevent PORC. The availability of sugammadex in Italian hospitals may have a beneficial impact on patient safety. This is due to the fact that PORC is a common and dangerous condition that may lead to postoperative inhalational events, hypoxemia, and pneumonia; and at the moment, it is not completely preventable even when advanced neuro-muscolar monitoring techniques are applied". In the case of rapid sequence intubation (RSI), rocuronium (1.2 mg/kg) administration followed by sugammadex represents a better choice in terms of efficacy and safety than succinylcholine. If a new drug is proven to be safer and more efficient than the one it is replacing, hospitals should consider the new drug and make it available, at least for selected patients or in situations at risk of severe complications. It is reasonable to hypothesize that, when discussing informed consent for elective procedures, patients and families may want to know if the admitting facilities have the superior agent available, and that the absence of such agent could create concerns and complains.

Self-directed deliberate practice with virtual fiberoptic intubation improves initial skills for anesthesia residents.

BACKGROUND: Fiberoptic intubation is a core skill in anesthesiology. However, this complex psychomotor skill is challenging to learn in the clinical setting. The goal of this study was to evaluate the Virtual Fiberoptic Intubation (VFI) software as an adjunct to the traditional fibreoptic intubation teaching. METHODS: After informed consent, 23 first year anesthesia residents with no previous experience of fiberoptic intubation were randomized to 2 groups. All subjects received an institutional didactic teaching session. The control group (N.=12) was taught by the usual didactic method only, while the VFI group (N.=11) had the same didactic teaching and also the opportunity to practice with VFI software for one week. Each resident was evaluated on their first oro- and nasotracheal fiberoptic intubations on a mannequin head. Each performance was evaluated by an expert bronchoscopist blinded to the previous type of teaching using a checklist score, a global rating scale (GRS) score and procedural time. RESULTS: The VFI group performed significantly better on the checklist and GRS scores compared to the control group for both the oral and nasal routes (all P<0.05). For procedural time, there was a trend towards faster performance in the VFI group compared to the control group for the oral route (P=0.05). There was no significant difference for procedural time between the VFI and the control groups when fiberoptic intubation was performed nasally (P=0.76). CONCLUSION: Self-directed practice using VFI software may improve the initial acquisition of fibreoptic intubation skills for anesthesia residents.

Ultrasound identification of nerve cords in the infraclavicular fossa: a clinical study.

BACKGROUND: This study aimed to analyze nerve trunk anatomy in the infraclavicular fossa and to correlate these data with the most common anthropometric parameters. METHODS: A Mylab 30 Gold (Esaote) and the linear transducer LA523 (7.5 MHz frequency) were used. The probe was oriented according to a parasagittal plane, parallel to the lateral chest wall and immediately medial to the coracoid process underneath the clavicle. Measurements included the distance between the artery and the cutaneous surface (mm) and the apical corner of the ultrasound image (mm), the number of identified nervous cords and their position related to the axillary artery, and the position and number of axillary veins. Sex, age, height, weight, body mass index (BMI), biceps girth, and breast size were recorded. Statistical analysis included calculation of linear Pearson correlation coefficient and Student's t test. RESULTS: Two hundred and two consecutive patients were enrolled. The position of the three cords was highly variable around the artery. In a small but significant percentage of patients (8.9%), the medial and the lateral cords were located together at the top of the artery. The visibility of the trunks and the distance between the upper part of the artery and the apical corner of the ultrasound image correlated with anthropometric characteristics. The vein position with respect to the artery and nerves was markedly variable. CONCLUSION: Sono-anatomic study of the infraclavicular region adds important data that is useful when conducting nerve blocks to improve safety and likelihood of success.

Cardiorenal syndromes and sepsis.

The cardiorenal syndrome is a clinical and pathophysiological entity defined as the concomitant presence of renal and cardiovascular dysfunction. In patients with severe sepsis and septic shock, acute cardiovascular, and renal derangements are common, that is, the septic cardiorenal syndrome. The aim of this paper is to describe the pathophysiology and clinical features of septic cardiorenal syndrome in light of the actual clinical and experimental evidence. In particular, the importance of systemic and intrarenal endothelial dysfunction, alterations of kidney perfusion, and myocardial function, organ "crosstalk" and ubiquitous inflammatory injury have been extensively reviewed in light of their role in cardiorenal syndrome etiology. Treatment includes early and targeted optimization of hemodynamics to reverse systemic hypotension and restore urinary output. In case of persistent renal impairment, renal replacement therapy may be used to remove cytokines and restore renal function.

Postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF) is common among surgical patients and associated with a worse outcome. Pathophysiology of POAF is not fully disclosed, and several perioperative factors could be involved. Direct cardiac stimulation from perioperative use of catecholamines or increased sympathetic outflow from volume loss/anaemia/pain may play a role. Metabolic alterations, such as hypo-/hyperglycaemia and electrolyte disturbances, may also contribute to POAF. Moreover, inflammation, both systemic and local, may play a role in its pathogenesis. Strategies to prevent POAF aim at reducing its incidence and ameliorate global outcome of surgical patients. Nonpharmacological prophylaxis includes an adequate control of postoperative pain, the use of thoracic epidural analgesia, optimization of perioperative oxygen delivery, and, possibly, modulation of surgery-associated inflammatory response with immunonutrition and antioxidants. Perioperative potassium and magnesium depletion should be corrected. The impact of those interventions on patients outcome needs to be further investigated.

Cefazolin bolus and continuous administration for elective cardiac surgery: improved pharmacokinetic and pharmacodynamic parameters.

OBJECTIVE: Cefazolin (1-2 g bolus at induction possibly repeated after cardiopulmonary bypass) remains the standard for antibiotic prophylaxis in cardiac surgery. Data indicate, however, that it is underdosed with this dosing schedule. A prospective, randomized study comparing intermittent versus loading dose plus continuous infusion for the same total dose of cefazolin was performed to assess which modality is pharmacokinetically and pharmacodynamically advantageous. METHODS: Patients received 2 g cefazolin as a starting dose and then were divided into an intermittent group (receiving another 1 g at 3, 9, and 15 hours after the first dose) and a continuous group (continuous infusion started after the first dose, providing 1 g every 6 hours for 18 hours). Cefazolin levels were measured in blood and atria. RESULTS: Mean total and calculated free trough concentrations in blood varied greatly among patients in the intermittent group and were lower than those in the continuous group (P < .05 at 15, 18 and 24 hours). For 9 of 10 (90%) patients in the continuous infusion group, the targeted pharmacokinetic and pharmacodynamic goal (time above minimal inhibitory concentration >90%) was achieved, whereas the goal was met for only 3 of 10 (30%) in the intermittent group (P < .05). The mean atrial tissue concentration was also higher with continuous infusion (P < .05). CONCLUSIONS: Administration of cefazolin as bolus plus continuous infusion has pharmacokinetic and pharmacodynamic advantages relative to intermittent administration. It provides more stable serum levels, lower interpatient variability, and higher myocardial tissue penetration.

Propofol sedation in a colorectal cancer screening outpatient cohort.

AIM: Colorectal cancer screening colonoscopies require sedation for both anxiety and pain. Propofol is used worldwide and allows for rapid and profound sedation with quick recovery after cessation of infusion. However, there is still a debate about whether it should be administered by anesthetists, gastroenterologists, or trained nurses. The aim of the study was to assess the number and proportion of patients who might benefit from the quality and safety of sedation under propofol during colonoscopies in a cohort of colorectal cancer screening outpatients. METHODS: Patients' genders, ages, numbers of operative procedures, and prior experience with colonoscopies were recorded, and differences were tested between sedated and unsedated patients. The need for mask ventilation and the rate of anesthetically, medically, or surgically related complications were compared between sedated and unsedated patients. The number of complete colonoscopies, length of the procedures, and time to reach the ileocecal valve were compared between sedated and unsedated patients. RESULTS: Of 135 colonoscopies, 101 were performed under sedation. All sedated patients underwent complete endoscopic examinations, while 8.9% of unsedated patients had their examination stopped due to excessive discomfort or pain. Colonoscopies tended to be shorter in sedated than unsedated patients. No anesthesia-related complications occurred. In 3/135 patients, a short period (<3 min) of mask ventilation was necessary. One surgical complication occurred among the sedated patients. One unsedated patient suffered a medical complication (dyspnea and ST-T elevation). CONCLUSIONS: Propofol sedation can be safely applied to colorectal cancer screening outpatients. Sedation was managed by a dedicated anesthetic staff and no patient suffered anesthesia-related complications.

Antioxidant therapy in critically septic patients.

Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. Recent studies pointed out the correlations between oxidative stress, systemic inflammatory response and apoptosis. Prospective randomized clinical trials regarding antioxidant therapy in critical illness provide increasing evidence in support of selenium, glutamine and omega-3 fatty acids. In particular selenium seems to improve clinical outcome in terms of infections and organ failure, glutamine has been associated with a significant reduction in infectious complications and omega-3 fatty acids could be particularly efficacious in sepsis. Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.

Acute severe arterial hypertension: therapeutic options.

Arterial hypertension is a very common condition. Cerebral, coronary and renal vessels are mainly affected by the deleterious effect of this condition, and both acute and chronic organ failure may ensue. Exacerbation of underlying pathophysiologic conditions or new precipitating factors can lead to hypertensive crisis, either urgencies or emergencies. During hypertensive emergencies, a quick raise in arterial pressure may lead to acute and significant organ dysfunction, such as aortic dissection, acute myocardial infarction, intracranial bleeding or acute renal failure. Perioperative hypertension often takes the shape of a crisis and it can be related to hypothermia, pain, neuro-hormonal response to surgical trauma or antihypertensive drugs withdrawal. Treatment for hypertensive crisis should achieve a progressive control of blood pressure, avoiding any abrupt decrease in organ blood supply. Therapeutic options are many and different in terms of pharmacokinetics and pharmacodynamic profiles. The best option should be based upon the characteristics of the patient and the pathophysiology of the hypertensive crisis. Of particular interest, some agents are metabolized by blood esterase and have a very short half life (e.g., clevidipine). This allows tight titration of their effect, which is advisable when carefully lowering blood pressure. This is of particular importance when treating hypertensive crisis in surgical patients both intra-operatively or in critical care.

Pathophysiology of sepsis in the elderly: clinical impact and therapeutic considerations.

The aging world population will increase the incidence and mortality of severe sepsis. The aim of the present article is to review the pathophysiological differences in sepsis and its clinical impact on the elderly. The impact of immunosenescence on innate and acquired immunity is associated with relative immunologic depression that may favor the spreading of inflammation. Elderly patients also have enhanced apoptotic pathways that may contribute to the incidence of mortality due to sepsis. The inflammation-coagulation network is activated by age, explaining the success of some specific therapies. The initial clinical picture of sepsis in the elderly may be ambiguous but the specific pathopysiological changes of aging increase the risk of a sudden deterioration to severe sepsis with the development of a serious cardiovascular dysfunction. The reduced stress tolerance characteristic of aged tissues explains the high incidence of multi-organ failure in such patients. The specific pathophysiological and clinical picture of sepsis underlies the increased mortality in such patients and prompts research on therapeutic strategies with particular benefits to elderly septic patients.

Changes in auditory evoked potentials induced by postsurgical sepsis.

BACKGROUND: Clinical examination may be less sensitive than electrophysiological methods in the diagnosis of sepsis-associated encephalopathy. The aim of this study was to evaluate the changes in A-line Autoregression Index (AAI) induced by postsurgical sepsis. METHODS: The study involved patients admitted to the University High Dependency Unit (HDU) after major abdominal surgery. Patients that later developed sepsis entered the septic group (SG), and the other patients formed the control group (CG). The SG underwent measurements of AAI and tests for bedside mental status, consciousness abnormalities, heart rate, blood pressure, respiratory rate, tympanic temperature and white blood cell concentration at HDU admission (T1) and within 6 hours after the diagnosis of sepsis was confirmed (T2). The CG was evaluated at T1 and at day 4 of the HDU stay. All measured variables were compared between CG and SG at T1 and T2 using the Mann Whitney test with a significance cut-off of P<0.001. RESULTS: The CG and SG included 30 and 24 patients, respectively. There was no difference between the CG and SG at T1. At T2, the median AAI was significantly higher in the CG than in the SG. Significant differences were found also for reactive protein C and body temperature. CONCLUSION: The occurrence of sepsis significantly reduces AAI. Measurement of AAI thus has the potential to be a reliable diagnostic test to identify subclinical sepsis-associated encephalopathy.

Acute left ventricular dysfunction due to Tako-tsubo syndrome after induction of general anesthesia.

Tako-tsubo cardiomyopathy is a recently described form of transient ventricular dysfunction that is not associated with coronary vessels obstruction, although its clinical manifestations are often similar to those of myocardial ischemia. This syndrome is possibly due to an excess of catecholamines, and it is associated with emotional and physical stress and surgery. However, the pathophysiological relation to anaesthesia has not yet been clarified. We report a case of Tako-tsubo cardiomyopathy that ensued immediately after induction of general anaesthesia for elective surgery in a patient submitted to laparoscopic cholecystectomy. The patient was first treated as if affected by myocardial ischemia, but a rapidly performed emergency coronary angiography showed normal epicardial coronary vessels with a significant reduction of left ventricular function. The coronary angiography ruled out the diagnosis of typical myocardial ischemia and allowed for the arrival at the correct diagnosis. The transient ventricular ballooning was attributed to the recently described Tako-tsubo syndrome. Prompt treatment allowed control of symptoms, and the patient was safely treated and discharged on day 15. Although it is difficult to identify the cause of this syndrome, it may be argued that, during general anaesthesia and particularly at induction, the imperfect control of catecholamine excess may induce cardiac damage in predisposed subjects.

State entropy and bispectral index: correlation with end tidal sevoflurane concentrations.

AIM: Aim of this study was to evaluate the difference between the correlations of state entropy (SE) and bispectral index (BIS) with different end tidal concentrations (Et) of sevoflurane. METHODS: A total of 40 ASA I/II patients submitted to abdominal surgery were enrolled in the study. After premedication with fentanyl, anesthesia was induced with propofol and atracurium and maintained with sevoflurane in oxygen and air. The values of Et sevoflurane, SE and BIS were recorded during the operating room stay. The mean Et sevoflurane was calculated and the correlations of SE and BIS with Et sevoflurane were determined with Pearson test separately at values of Et sevoflurane below and higher the mean Et sevoflurane. Student's t-test was used to verify if the difference between the correlations was significant (P<0.05). RESULTS: The mean Et sevoflurane was 1.5%. During anesthesia the correlation with Et sevoflurane was -0.75 for SE and -0.70 for BIS. At Et sevoflurane higher than 1.5% the correlation with Et sevoflurane was -0.41 for SE and -0.14 for BIS. At Et sevoflurane below 1.5% the correlation with Et sevoflurane was -0.65 for SE, and -0.8 for BIS. The difference between the correlations of Et sevoflurane with SE and BIS resulted statistically significant. CONCLUSION: During sevoflurane anesthesia SE shows a better correlation than BIS with Et sevoflurane. Although at low Et sevoflurane the correlation is better with BIS, at high Et sevoflurane the correlation is better with SE.

Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units.

AIM: Continuous monitoring is of paramount importance in order to obtain a correct level of sedation in ICU patients. Clinical scoring systems, although simple and inexpensive, are often inadequate in evaluating the patient level of consciousness. Among instrumental tools for sedation monitoring, Bispectral Index (BIS) is now widely used due to its reliability and applicability. Nevertheless some doubts still exist regarding its usefulness in ICU. METHODS: Sedation, obtained with propofol or midazolam, was monitored with Ramsay scale and BIS in 40 patients admitted in ICU for postoperative monitoring after major abdominal or vascular surgery. A correlation between Ramsay score and BIS values was searched using Pearson test. RESULTS: A good correlation between Ramsay score and BIS values was observed. At the deeper levels of sedation a wide range of BIS values corresponds to Ramsay score 6, indicating various levels of central nervous system depression that are not identified by clinical evaluation. CONCLUSIONS: BIS monitoring is useful in ICU patients and allows a finest differentiation of sedation level in deeply sedated ICU patients.