Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study.

BACKGROUND: Acetaminophen (ACT) has been studied in septic patients with detectable plasmatic levels of cell-free hemoglobin (Hb), where it demonstrated to inhibit the hemoprotein-mediated lipid peroxidation and oxidative injury, with a potential of beneficial effect on the endothelium. On the basis of this background, the aim of this study was to evaluate the sublingual microcirculation and the peripheral tissue perfusion before-and-after administration of ACT on clinical judgment in a cohort of febrile septic and septic shock patients. METHODS: Prospective observational study. 50 adult septic and septic shocks treated with ACT for pyrexia, where the sublingual microcirculation and the peripheral tissue perfusion with Near Infrared Spectroscopy (NIRS) and vascular occlusion test (VOT) were evaluated before ACT (t0), after 30 min (t1) and after 2 h (t2). Cell-free Hb and the markers of oxidative stress and endothelial damage were measured at t0 and t2. RESULTS: The study showed a significant increase of the density of the perfused small and total vessels of the sublingual microcirculation 30 min after the infusion of ACT; it also showed an increase of the Microvascular Flow Index (MFI) and a decrease in the heterogeneity of the flow. At a peripheral muscular level, we found an acceleration in the reperfusion curve after VOT at t1, expression of a higher reactivity of the microvasculature. CONCLUSIONS: ACT infusion did not show a clear correlation with cell-free Hb; however, it exhibited protective effect toward the microcirculation that was evident in particular in septic patients. This correlation merits further exploration.

Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock.

BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. METHODS: Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. RESULTS: 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. CONCLUSIONS: Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. TRIAL REGISTRATION: NCT02750163.

The Bonfils fiberscope: a clinical evaluation of its learning curve and efficacy in difficult airway management.

BACKGROUND: This study evaluated the use of the Bonfils fiberscope by analyzing its learning curve, efficacy and safety during airway management. METHODS: This was a prospective observational study where five anesthetists, with differing levels of experience, were asked to use the Bonfils rigid fiberscope (Karl Storz) for a six-month period. They used the scope when performing endotracheal intubations in patients undergoing general anesthesia. The patients were excluded if various clinical indicators predicted that they might be difficult to intubate. The patient's head was kept in the neutral position to simulate the intubation of a trauma patient. Direct laryngoscopy with a Macintosh blade was performed to assign a Cormack and Lehane grade prior to attempting laryngoscopy with the Bonfils fiberscope. After intubating the patient with the Bonfils fiberscope, intubation time and any complications or failures noted after the procedure were recorded. RESULTS: The study included 216 patients, three of which were failed intubations. No complications occurred during the study period. The median intubation time was 21.4 s. The learning curve improved significantly after 20 intubations (P<0.05) and was affected by the operator's experience and aptitude with endoscopic viewing. Seventeen patients were deemed to have "unpredicted" difficult airways: 15 subjects with a Cormack grade 3 (6.9%) and two subjects with a Cormack 4 (0.9%). Median time to intubation in subjects with a Cormack <3 was 16 s (95% CI=10-29 s), and in subjects with a Cormack ≥3, it was 15 s (CI 95%=15-18 s) with P=0.703. CONCLUSION: The Bonfils fiberscope is an efficient, easy to use and safe device for endotracheal intubation.

[Safety Walkround as a risk assessment tool: the first Italian experience]. / La Safety WalkRoundTM un'opportunità per l'assessment del rischio: la prima esperienza italiana.

In 2007 the Study Group "Clinical Risk Management" of the Italian Society of Anaesthesia and Intensive Care Unit (SIAARTI) performed a multicentric study in Intensive Care Unit (ICU) to assess the feasibility and efficacy of the Safety WalkRound (SWR) as a tool for the risk assessment. As the environment and organization of ICU are more complex than anaesthesia ones, mainly due to the severity of patients, high number of involved healthcare givers and different kinds of procedures, the Study Group decided that a check list is not fit for ICU and , after a careful review of the literature, chose to test the Safety WalkRound. in four Italian General ICUs. The SWR was born in 2003 when Frankel plans a structured interview of 15 questions (about 50% open) to collect operators' opinion about rate and type of errors, near misses, communication, problems regarding the report of adverse events and suggestions to increase patient safety. Consequently SWR is a tool of risk assessment alternative to the Incident Reporting which is marked by a diffuse underreporting of operators. Although the SWR is a new tool not validated in Italian language neither published in Italy on PubMed journals , the Study Group has decided that it might be fit for the organization of Italian Healthcare System. A back translation of the validated model of Joint Commission was provided and the translated version has been lightly changed to be employed in hospitals with and without Incident Reporting . The questions have been changed or introduced on the basis of the organization vulnerabilities detected with observational techniques or Focus Group. The interview performed in Italy contains 16 questions classified into five groups: a) error, b) error prevention, c) communication, teamwork and leadership, d) error discussion and e) relationship with patients and their families. The answers collected have been analyzed to detect the vulnerabilities in the organizations and specify the improvements to implement in every ICU. A statistical analysis was performed to verify the correlation between the answers collected and the results of the other techniques of risk assessment previously used ( observations and Focus Group ) . The value of k Pearson found ( mean value 0,976) has demonstrated this correlation and the efficacy of SWR in detecting system vulnerabilities already found with the other assessment techniques. The value of a Cronbach ( mean value 0,798) has demonstrated an internal consistency reliability. The results of this study have demonstrated that the Italian translation is fit for the model by Frankel and makes available a lot of information useful to improve patient safety. The study has demonstrated the sensibility, efficacy and efficiency of this tool in detecting the vulnerabilities in every ICU of the four ones. SWR is marked by feasibility, high compliance of operators and low costs; besides increases safety culture in the staff and demonstrating.

A new and feasible model for predicting operative risk.

BACKGROUND: Although the POSSUM (Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity) score can be used to calculate operative risk, its complexity makes its use unfeasible in the immediate clinical setting. The aim of this study was to create a new model, based on ASA status, to predict mortality. METHODS: Data were collected in two hospitals. All types of surgery were included except for cardiac surgery and Caesarean delivery. Age, sex and preoperative information, including the presence of cardiocirculatory and/or lung disease, renal failure, diabetes mellitus, hepatic disease, cancer, Glasgow Coma Score, ASA grade, surgical diagnosis, severity of the procedure and type of surgery (elective, urgent or emergency), were recorded for each patient. The model was developed using a data set incorporating data from 1936 surgical patients, and validated using data from a further 1849 patients. Forward stepwise logistic regression was used to build the model. Goodness of fit was examined using the Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve analyses were performed on both data sets to test calibration and discrimination. In the validation data set, the new model was compared with POSSUM and P-POSSUM for both calibration and discrimination, and with ASA alone to compare discrimination. RESULTS: The following variables were included in the new model: ASA status, age, type of surgery (elective, urgent, emergency) and degree of surgery (minor, moderate or major). Calibration and discrimination of the new model were good in both development and validation data sets. This new model was better calibrated in the validation data set (Hosmer-Lemeshow goodness-of-fit test: chi(2)=6.8017, P=0.7440) than either P-POSSUM (chi(2)=14.4643, P=0.1528) or POSSUM, which was not calibrated (chi(2)=31.8147, P=0.0004). POSSUM and P-POSSUM had better discrimination than the new model, although this was not statistically significant. Comparing the two ROC curves, the new model had better discrimination than ASA alone (difference between areas, 0.077, SE 0.034, 95% confidence interval 0.012-0.143, P=0.021). CONCLUSIONS: This new, ASA status-based model is simple to use and can be performed routinely in the operating room to predict operative risk for both elective and emergency surgery.

[Functional urination disorders in patients recovering in an intensive care unit for more than 30 days]. / I disturbi funzionali della minzione in pazienti ricoverati in unità di terapia intensiva (ICU) per più di 30 giorni.

Patients in rest-homes, intensive care units, long hospitalization and dialysis and whoever stays in a hospital continuously or occasionally for long periods of time may run into the well-known and typical complications of prolonged hospitalization. We have studied the urologic aspect in all the cases of the Medical- Surgical Emergency Institute in the Hospital of Ancona (seated in Torrette), over the period 1990-96, in patients hospitalized for at least 30 days. All the patients were followed and studied with the same method, though taking into account their different pathological conditions. They were treated by the same medical and paramedical staff. The same antibiotic therapy and the same checkup were adopted for all of them. We have noticed that out of 122 patients the most frequent pathologies have been urinary infections (19%); while sepsis with different pathogenesis was recorded in 4% of the patients. The method of study applied during and after the hospitalization was used also in rehabilitation centres and included: urologic examination, rectal touch (in men), direct X-ray of the abdomen, ultrasound of the urinary tract, X-ray urography, if required; moreover urodynamic examination, MRI of encephalon and spinal marrow in patients with neurological lesions. The catheter was removed in all the patients and none of the following conditions were observed: vesical lithiasis, abscesses, fistulae in penoscrotal angle, urethrostenosis, injuries to renal emunctory. In conclusion we believe that the functional symptoms of minction--be they of obstructive or irritable nature--are not existent and that the urologic prognosis in long term patients in excellent, provided that prophylaxis is carried on against hospital urinary infections as their occurrence is very frequent and therapy is expensive. It can also be stated the patient hospitalized in ICU will not present damages to the urinary tract, even if he/she has been hospitalized because of injuries to the urinary tract, provided that the urologic tutoring, together with the action of the physician handling the Emergency, follow the rules for asepsis, the best biocompatible materials are use, infections are monitored, the extensions of cerebrospinal injuries are examined and therapeutic axioms, such as barren and clean intermittent catheterism, are finally adopted.

Predictive value of interleukin 6 (IL-6), interleukin 8 (IL-8) and gastric intramucosal pH (pH-i) in major abdominal surgery.

OBJECTIVE: To study plasma concentrations of interleukin 6 (IL-6) and interleukin 8 (IL-8) in patients with splanchnic hypoxia, as documented by gastric intramucosal measurements (pH-i), during major abdominal surgery and the relationship between IL-6 and IL-8 concentrations and postoperative complications as well as clinical outcome. DESIGN: A prospective study. PATIENTS: Twelve patients scheduled for major abdominal surgery with no evidence of coexisting infectious disease. RESULTS: Six out of seven samples from patients with postoperative complications showed intraoperative pH-i levels lower than 7.32 and IL-6 levels higher than 300 pg/ml. Seven out of nine samples from patients without complications showed pH-i levels higher than 7.32 and IL-6 levels lower than 300 pg/ml. The difference in the pattern of distribution was statistically significant (p < 0.01). Only two out of seven samples of patients with postoperative complications showed intraoperative pH-i levels lower than 7.32 and IL-8 levels higher than 60 pg/ml. It was not possible to identify a clear distribution pattern of data points for IL-6 and IL-8 during the postoperative period. CONCLUSIONS: Intraoperative splanchnic ischemia, as documented by gastric intramucosal pH-i, is directly correlated to the increase of IL-6 plasma levels and to the incidence of postoperative complications, while IL-8 levels showed no correlation with surgical complications.

[Predictivity associated with oxygen-transporting hemodynamic parameters: relation between the cardiac index and oxygen extraction]. / Predittività associata a parametri emodinamici ossiforetici: relazione tra l'indice cardiaco e l'estrazione di ossigeno.

OBJECTIVE: To verify the predictivity of a diagram with the cardiac index (CI) on the y-axis and the oxygen extraction (O2ER) on the x-axis and to verify if the haemodynamic therapy could change the outcome. DESIGN: A retrospective study on a consecutive series of patients. SETTING: University Intensive Care Unit of Ancona. SUBJECTS: 65 critically ill patients, subdivided in survivors (38) and non survivors (27). INTERVENTIONS: All the patients have been monitored with a Swan-Ganz catheter. MEASUREMENTS: CI and O2ER at the admission (T0), at 12 (T1), 24 (T2) and 48 hours (T3) from T0. The diagram CI/02ER has been subdivided in 9 parts on the basis of the normal values of CI (> or = 2,5 and < or = 3,5 1/min/m2) and of O2ER (< or = 24 and > or = 28%). RESULTS: At T2 most of survivors (73.7%) is on the most favourable part of the diagram, with the CI and the O2ER normal or increased, while only 21.4% of non survivors is in this part. On the contrary only 26.3% of survivors versus 78.6% of non survivors are in the less favourable part of the diagram. The chi 2-test shows a good significantly (p = 0.003) in the different distribution on the diagram between survivors and non survivors. A 2 x 2 table has been made. We found: sensibility 78.6% specificity 73.7% and total correct 75.4%. In any other time it has been found a significant different distribution on the diagram between survivors and non survivors. CONCLUSIONS: This diagram can be useful to predict the short term outcome in non septic patients, because at 24 hours give a correct prediction of the outcome in 3 patients on 4, with a good prediction either of the good outcome or of the exitus.

[Intraoperative lactic acidosis, can it be treated? Clinico-experimental, prospective, sequential study]. / A proposito di acidosi lattica intraoperatoria, è possibile trattarla? Studio clinico-sperimentale, prospettico, sequenziale.

OBJECTIVE: To verify the efficacy and absence of risk attributable to therapy with alkaline solutions for correction of lactic acidosis and to demonstrate the usefulness of L-carnitine in converting lactate into pyruvate in conditions of good blood oxygenation. DESIGN: Prospective study on a consecutive series of patients subdivided into three groups following the use of: alkalinizing therapy (group I), L-carnitine (group II), or saline solution (group III). Groups 1 and 2 were further subdivided into subgroups "a" and "b" according to the type of alkalinizing agent and of L-carnitine somministration. SETTING: Teaching Hospital-Torrette di Ancona. PATIENTS: 65 patients submitted to major vascular surgery with aortic clamping in the time period between January 1992 and August 1993. INTERVENTIONS: During aortic clamping patients of: group I received 2 mEq:kg of bicarbonate or tromentamolo according to the specific subgroup. Group II received a bolus of 2 g of L-carnitine, patients of group IIb received further 2 g of carnitine in continuous perfusion until the end of surgery. Group III received no pharmacological intervention. MEASUREMENTS: HR BP, arterial blood gases and lactic acid levels were measured at 12 pre-determined times. RESULTS: Only a neutralizing effect of alkalinizing therapy was observed, whereas the lactic acid measurements demonstrated no significant differences between the different groups. CONCLUSIONS: These results confirm the data of other Authors concerning the good compliance of alkalinizing therapy, however, there was demonstrated no clear evidence of its effective usefulness. No metabolic stimulation due to L-canitina could be demonstrated in our experimental conditions.