Francesco Forfori

Fluid balance and urine volume are independent predictors of mortality in acute kidney injury

IntroductionIn ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI.MethodsWe performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression.ResultsOf the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001).ConclusionsIn this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.

Risk factors assessment of the difficult airway: An Italian survey of 1956 patients

Over the last decade, there has been a heightened awareness and an increase in the amount of literature being published on recognition and prediction of the difficult airway. During the preoperative evaluation of the airway, a thorough history and physical specifically related to the airway should be performed. Various measurements of anatomic features and noninvasive clinical tests can be performed to enhance this assessment. In this study we correlated the Mallampati modified score and several other indexes with the laryngoscopic view to identify anatomical and clinical risk factors related to the difficult airway. We prospectively collected data on 1956 consecutive patients scheduled to receive general anesthesia requiring endotracheal intubation for elective surgery. The Mallampati classification versus the Cormack-Lehane (C-L) linear correlation index was 0.904. A Mallampati Class 3 correlated with a C-L Grade 2 (0.94), whereas a Mallampati Class 4 correlated with a C-L Grade 3 (0.85) and a C-L Grade 4 (0.80). Operator evaluation, performed by a simplified tracheal intubation difficulty scale, showed a linear correlation of 0.96 compared with the C-L groups. Although there is a correlation between oropharyngeal volume and difficult intubation, the Mallampati score by itself is insufficient for predicting difficult endotracheal intubation.

Antioxidant and neuroprotective properties of blueberry polyphenols: a critical review

Abstract Objective The aim of this work was to highlight the effects and the possible mechanisms of the action of blueberry polyphenols on the central nervous system (CNS). Methods An analysis was carried out, in a temporal order, of the most important literature about this topic and the results have been correlated with the beneficial and protective effects, mainly concerning the CNS. Discussion Over the last 10 years an increasing scientific interest has developed about polyphenols, which are very abundant in blueberries, as they have been seen to produce favourable effects related to neuroprotection and linked to a possible decrease of age-related cognitive and motor decline, as shown by the improvement of such functions in animal models with a supplemented diet. Such effects could not only be explained through a purely antioxidant action but also through more complex mechanisms related to inflammation, genic expression, and regulation of cell survival. Conclusions Despite the wealth of data from animal studies, there is a relative lack of data concerning human beings, even if some positive results are beginning to emerge. Therefore, blueberry polyphenols could become useful pharmacological agents for various conditions including neurological diseases, but further studies are still necessary to attain this objective.

Morphological evidence that xenon neuroprotects against N-methyl-DL-aspartic acid-induced damage in the rat arcuate nucleus: a time-dependent study.

Abstract:  The hyperactivation of glutamate receptors, especially those of the N‐methyl‐d‐aspartate subtype (NMDA), can induce excess calcium entry into cells, leading to neuronal death. Since the anesthetic gas xenon behaves as an NMDA antagonist, the present article investigated, by distinct morphological approaches and after different times, the possible neuroprotectant effects of this gas in a model of neuronal damage induced by N‐methyl‐dl‐aspartic acid (NMA) on rat arcuate nucleus. Rats were assigned to the following groups: controls; xenon exposure; NMA treatment; or xenon exposure + NMA treatment. Animals were placed in an experimental cage and after 10 min a mixture of xenon (or nitrogen) 70% and oxygen 30% was delivered. After 3 h, 1, 2, 5, or 7 days from gas exposure, rats were euthanized and the whole brain was removed and processed for either transmission electron microscopy or light microscopy. In the arcuate nucleus from NMA‐treated animals only 40–60% of cell population survived in all times with several degenerating neurons giving the typical appearance of a “bulls eye.” At ultrastructural level, chromatin margination, nuclear shrinkage, mitochondria with matrix dilution, dilated endoplasmic cisternae, and electrondense cytoplasm were detected. Xenon alone did not induce changes, but reduced of about 50% NMA‐induced cell loss as well as degenerating neurons, with the maximal neuroprotection at 7 days. These results confirm that in the rat arcuate nucleus NMA can induce a severe neuronal damage that is already marked after 3 h. Xenon significantly reduced the neuronal damage at all times and can be then regarded as a promising neuroprotectant agent.

Jugular vein distensibility predicts fluid responsiveness in septic patients

IntroductionThe purpose of the study was to verify the efficacy of using internal jugular vein (IJV) size and distensibility as a reliable index of fluid responsiveness in mechanically ventilated patients with sepsis.MethodsHemodynamic data of mechanically ventilated patients with sepsis were collected through a radial arterial indwelling catheter connected to continuous hemodynamic monitoring system (Most Care®, Vytech Health, Padova, Italy), including cardiac index (CI) (L/min/M2), heart rate (beats/min), mean arterial pressure (MAP) (mmHg), central venous pressure (CVP) (mmHg) and arterial pulse pressure variation (PPV), coupled with ultrasound evaluation of IJV distensibility (%), defined as a ratio of the difference between IJV maximal antero-posterior diameter during inspiration and minimum expiratory diameter to minimum expiratory diameter x100. Patients were retrospectively divided into two groups; fluid responders (R), if CI increase of more than or equal to 15% after a 7 ml/kg crystalloid infusion, and non-responders (NR) if CI increased more than 15%. We compared differences in measured variables between R and NR groups and calculated receiver-operator-characteristic (ROC) curves of optimal IJV distensibility and PPV sensitivity and specificity to predicting R. We also calculated a combined inferior vena cava distensibility-PPV ROC curve to predict R.ResultsWe enrolled 50 patients, of these, 30 were R. Responders presented higher IJV distensibility and PPV before fluid challenge than NR (P <0.05). An IJV distensibility more than 18% prior to volume challenge had an 80% sensitivity and 85% specificity to predict R. Pairwise comparison between IJV distensibility and PPV ROC curves revealed similar ROC area under the curve results. Interestingly, combining IJV distensibility more than 9.7% and PPV more than 12% predicted fluid responsiveness with a sensitivity of 100% and specificity of 95%.ConclusionIJV distensibility is an accurate, easily acquired non-invasive parameter of fluid responsiveness in mechanically ventilated septic patients with performance similar to PPV. The combined use of IJV distensibility with left-sided indexes of fluid responsiveness improves their predictive value.

Utilization of Small Changes in Serum Creatinine with Clinical Risk Factors to Assess the Risk of AKI in Critically lll Adults

BACKGROUND AND OBJECTIVES Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patients clinical course. We set out to assess the performance of this combination approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1-0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit. RESULTS Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for severe AKI was 92%, the specificity was 62%, the positive predictive value was 16%, and the negative predictive value was 99%. After adjustment for Sequential Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early creatinine elevation remained an independent predictor for severe AKI (adjusted relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early creatinine elevation to the best clinical model improved prediction of the primary outcome (area under the receiver operating characteristic curve increased from 0.75 to 0.83, P<0.001). CONCLUSION Critically ill patients at high AKI risk, based on the combination of clinical factors and early creatinine elevation, are significantly more likely to develop severe AKI. As initially hypothesized, the high-risk combination group methodology can be used to identify patients at low risk for severe AKI in whom AKI biomarker testing may be expected to have low yield. The high risk combination group methodology could potentially allow clinicians to optimize biomarker use.

Rapid Reversal of Severe Lactic Acidosis After Thiamine Administration in Critically Ill Adults A Report of 3 Cases

BACKGROUND Thiamine plays a critical role in energy metabolism. Critically ill patients may have thiamine deficiency and increased mortality due to potentially irreversible consequences. The aim of this study was to show the impact of thiamine deficiency in a series of patients and the rapid response to thiamine replacement, showing the changes in clinical and metabolic conditions over time. METHODS We described 3 cases of hospitalized patients who had received parenteral nutrition (PN) without vitamin supplementation. All the patients were admitted to the ICU between 2010 and 2011 with a severe form of lactic acidosis, an unstable circulatory state, and a different neurological disorder (a lethargic state, a severe form of impaired near-coma consciousness, and Wernicke encephalopathy). RESULTS Intravenous (IV) administration of thiamine was associated with a rapid and marked restoration of acid-base balance, hemodynamic stability and the disappearance of neurological disturbances, and normalization of the clinical and biochemical conditions of all the patients within the following hours. CONCLUSIONS The 3 cases demonstrated the rapidity of the reversal of severe thiamine deficiency, achieved by appropriate replacement in different hospitalized patients. The regression of clinical and biochemical disorders requires a prompt diagnosis and treatment based on the IV administration of thiamine and magnesium sulfate. In hospitalized patients at risk, thiamine deficiency is prevented by the integration of thiamine supplementation into PN and other forms of nutrition support.

Xenon Anesthesia Improves Respiratory Gas Exchanges in Morbidly Obese Patients

Background. Xenon-in-oxygen is a high density gas mixture and may improve PaO2/FiO2 ratio in morbidly obese patients uniforming distribution of ventilation during anesthesia. Methods. We compared xenon versus sevoflurane anesthesia in twenty adult morbidly obese patients (BMI > 35) candidate for roux-en-Y laparoscopic gastric bypass and assessed PaO2/FiO2 ratio at baseline, at 15 min from induction of anaesthesia and every 60 min during surgery. Differences in intraoperative and postoperative data including heart rate, systolic and diastolic pressure, oxygen saturation, plateau pressure, eyes opening and extubation time, Aldrete score on arrival to the PACU were compared by the Mann-Whitney test and were considered as secondary aims. Moreover the occurrence of side effects and postoperative analgesic demand were assessed. Results. In xenon group PaO2-FiO2 ratio was significantly higher after 60 min and 120 min from induction of anesthesia; heart rate and overall remifentanil consumption were lower; the eyes opening time and the extubation time were shorter; morphine consumption at 72 hours was lower; postoperative nausea was more common. Conclusions. Xenon anesthesia improved PaO2/FiO2 ratio and maintained its distinctive rapid recovery times and cardiovascular stability. A reduction of opioid consumption during and after surgery and an increased incidence of PONV were also observed in xenon group.

Comparison Between Doppler-echocardiography and Uncalibrated Pulse Contour Method for Cardiac Output Measurement: A Multicenter Observational Study*

Objectives: Echocardiography and pulse contour methods allow, respectively, noninvasive and less invasive cardiac output estimation. The aim of the present study was to compare Doppler echocardiography with the pulse contour method MostCare for cardiac output estimation in a large and nonselected critically ill population. Design: A prospective multicenter observational comparison study. Setting: The study was conducted in 15 European medicosurgical ICUs. Patients: We assessed cardiac output in 400 patients in whom an echocardiographic evaluation was performed as a routine need or for cardiocirculatory assessment. Interventions: None. Measurements and Main Results: One echocardiographic cardiac output measurement was compared with the corresponding MostCare cardiac output value per patient, considering different ICU admission categories and clinical conditions. For statistical analysis, we used Bland-Altman and linear regression analyses. To assess heterogeneity in results of individual centers, Cochran Q, and the I 2 statistics were applied. A total of 400 paired echocardiographic cardiac output and MostCare cardiac output measures were compared. MostCare cardiac output values ranged from 1.95 to 9.90 L/min, and echocardiographic cardiac output ranged from 1.82 to 9.75 L/min. A significant correlation was found between echocardiographic cardiac output and MostCare cardiac output (r = 0.85; p < 0.0001). Among the different ICUs, the mean bias between echocardiographic cardiac output and MostCare cardiac output ranged from –0.40 to 0.45 L/min, and the percentage error ranged from 13.2% to 47.2%. Overall, the mean bias was –0.03 L/min, with 95% limits of agreement of –1.54 to 1.47 L/min and a relative percentage error of 30.1%. The percentage error was 24% in the sepsis category, 26% in the trauma category, 30% in the surgical category, and 33% in the medical admission category. The final overall percentage error was 27.3% with a 95% CI of 22.2–32.4%. Conclusions: Our results suggest that MostCare could be an alternative to echocardiography to assess cardiac output in ICU patients with a large spectrum of clinical conditions.

Evaluation of a preoperative pain score in response to pressure as a marker of postoperative pain and drugs consumption in surgical thyroidectomy.

Introdution:The success and effectiveness of a day surgery model are essentially related to a good postoperative course with a rapid recovery. Adequate management of analgesia during the hospital stay and after discharge becomes mandatory in reducing postoperative patient discomfort, and in facilitating discharge to home. Background:The aim of this study was to identify the efficacy of preoperative visual analog scale (VAS) score in predicting postoperative pain and analgesic drugs consumption. The hypothesis of a significant relation between preoperative pain and postoperative pain tolerance thresholds was tested using Spearman rank-order correlations, applied to patients scheduled for thyroidectomy in a Day Surgery Unit. Methods:Patients scheduled for total thyroidectomy underwent a preoperative pain test to assess the VAS value after a fixed stimulus (inflation of a sphygmomanometer with a pressure of 250 mm Hg). To estimate the power of the VAS in prediction of the postoperative analgesic requests, we divided the patients into 3 groups according to the preoperative VAS values (A group, including all patients with preoperative VAS⩽3; B group including patients with preoperative VAS>3⩽6; C group with preoperative VAS>6).Then we correlated preoperative results with postoperative VAS values and postoperative analgesic drug consumption, analyzing the correlation between the sensitivity and the specificity of the VAS test for a range of different cutoff values. Results:Thirty-two patients were included. A group (10 patients) showed a medium postoperative VAS<4, and required less analgesics than other groups (ketorolac, 51 mg). B group (10 patients) and C group (12 patients) showed higher postoperative VAS value and required more analgesic drug (B, 80 mg; C, 90 mg+1 g acetaminophen). Using the receiver operating characteristic or relative operating characteristic examination and calculating the underlying area , we could measure the discriminating ability of the test and found that the best VAS score cutoff was 3. Conclusion:The use of a preoperative test to assess individual pain threshold may be predictive for postoperative pain and analgesic request. The mathematical and statistical model used in this study confirms that a difference in the value of VAS of 3 shall be mathematically eligible for analgesia treatment.