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.

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).

Sedation in PACU: indications, monitoring, complications.

The aim of the present article is to review the indications, the monitoring and the complications of sedation in the post-anaesthesia care unit (PACU). In this setting, sedation is often an unwanted side effect of anaesthetic drugs that delay discharge, however it could be specifically indicated. Such indications include postoperative anxiety and agitation, airway management and mechanical ventilation, protection against myocardial ischaemia and intracranial hypertension control. Whenever sedation is used, an appropriate monitoring is useful to achieve an adequate level for the specific indication. Methods for sedation monitoring in PACU may be subjective (clinical scales) or objective (lower oesophageal sphincter contractility measurement, heart rate variability, evoked potentials and parameters derived from the electroencephalogram). The target score of the most common clinical scales has been reviewed according to the specific indication. An adequate monitoring is fundamental to avoid the complications of sedation including bradycardia, hypotension, prolonged mechanical ventilation and increased risk of respiratory tract infection as pointed out by many recent data. Therefore, sedation should be used carefully and with an adequate monitoring in post-operative patients not to affect negatively morbidity and mortality.

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.

Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome.

This study investigates the effects of N-acetylcysteine (NAC) and rutin on the lung oxidative burden of patients with early adult respiratory distress syndrome (ARDS). The protection was evaluated by measuring expired ethane and malondialdehyde (MDA), and oxidized (GSSG) and reduced glutathione (GSH) in the epithelial lining fluid of 36 patients who developed ARDS less than 24 hours before enrollment in the study. The patients were randomly assigned to 3 groups, receiving 250 mL 5% dextrose in water (group 1), NAC 50 mg/kg body weight in 5% dextrose (group 2), and NAC 50 mg/kg + rutin 5 mg/kg in 5% dextrose (group 3). Ethane and MDA concentrations were significantly reduced in the treatment groups after day 6. GSH was 30% increased in the treatment groups. No significant variations were observed in the control group until day 9. The trial confirms that NAC and rutin are efficient in protecting the lungs of patients with ARDS.

Microalbuminuria as an early index of impairment of glomerular permeability in postoperative septic patients.

OBJECTIVE: To evaluate whether microalbuminuria increases in post-operative patients developing sepsis, and whether it is correlated to the sepsis severity score (SOFA) and the PaO2/FIO2 ratio. DESIGN: Prospective study. SETTING: University intensive care unit. PATIENT POPULATION: Fifty-five postoperative ASA II-III patients admitted to the ICU after major abdominal or vascular surgery. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Urine collection and measurement of microalbuminuria and urinary creatinine on admission and again as soon as sepsis developed or at the end of the study (72 h after admission). Results are expressed as the microalbuminuria/creatinine ratio (MACR). The MACR significantly increased as soon as sepsis (defined according to the ACPP/SCCM Consensus Conference) appeared. The MACR positively correlated to the SOFA score, but had no relation to the PaO2/FIO2 ratio. Patients not developing sepsis did not show any increase in the MACR during the study period. CONCLUSIONS: Post-operative patients developing sepsis, unlike those with an uncomplicated postoperative evolution, showed an increase in glomerular permeability which was revealed by MACR. The increase in the MACR was positively correlated to the increase in SOFA score, while it had no relation to the PaO2/FIO2 ratio.

Device-related infections in critically ill patients. Part I: Prevention of catheter-related bloodstream infections.

Device utilization in critically ill patients is responsible for a high risk of complications such as catheter-related bloodstream infections (CRBSI), ventilator-associated pneumonia (VAP) and urinary tract infections (UTI). In this article we will review the current status of data regarding CRBSI prevention. General recommendations include staff education and use of a surveillance program with a restrictive antibiotic policy. Adequate time must be allowed for hand washing and barrier precautions must always be used during device manipulation. The routine changing of central catheters is not necessary and increases costs; it is necessary to decrease the handling of administration sets, to use a more careful insertion technique and less frequent set replacement. Antiseptic-coated catheters appear to reduce catheter colonization but their ability to prevent catheter-related infections requires further demonstration. More clinical trials are needed to verify the efficacy of measures to prevent CRBSI.

What is the role of streptogramins in intensive care?

The combination of two injectable streptogramins, quinupristin/dalfopristin, provides a new pharmacological choice proven to be therapeutically efficacious against most Gram-positive, multi-resistant microorganisms. They have been shown to be efficacious above all in critically ill patients hospitalized in intensive care who have unique alterations in homeostasis that makes tissue penetration of various pharmacological antimicrobials difficult. In cases of infection localized in difficult-to-treat sites, the combination with other drugs, such as cefepime, a glycopeptide or linezolid, is able to potentiate the action of the streptogramin with positive results which allow resolution of the illness. In this article, we review data from the literature on the use of quinupristin/dalfopristin in the treatment of Gram-positive, multi-resistant infections in critically ill patients.

Device-related infections in critically ill patients. Part II: Prevention of ventilator-associated pneumonia and urinary tract infections.

Device utilization in critically ill patients is responsible for a high risk of complications such as catheter-related bloodstream infections (CRBSI), ventilator-associated pneumonia (VAP) and urinary tract infections (UTI). In this article we will review the current status of data regarding the prevention of VAP and UTI. The results of the more recent (5 years) randomized controlled trials are reviewed and discussed. General recommendations include staff education and use of a surveillance program with a restrictive antibiotic policy. Adequate time must be allowed for hand washing and barrier precautions must always be used during device manipulation. Specific measures for VAP prevention are: 1) use of multi-use, closed-system suction catheters; 2) no routine change of the breathing circuit; 3) lubrication of the cuff of the endotracheal tube (ET) with a water-soluble gel; 4) maintenance of patient in semi-recumbent position to improve chest physiotherapy in intubated patients. Specific measures for UTI prevention include: 1) use of a catheter-valve instead of a standard drainage system; 2) use of a silver-alloy, hydro gel-coated latex urinary catheter instead of uncoated catheters. Biofilm represents a new variable: the capacity of bacteria to organize a biofilm on a device surface can explain the difficulty in preventing and eradicating an infection in a critically ill patient. More clinical trials are needed to verify the efficacy of prevention measures of ICU infections.

Therapeutic use of albumin.

The clinical use of albumin solutions is a controversial issue, that involves albumin as a volume plasma expander, a supplement of total parenteral nutrition and a substance with pharmacological properties. The aim of this review is to show the present role of albumin in the clinical setting. We reviewed experimental and clinical data collected by the Medline System and the bibliographies of relevant articles. Experimental studies were selected on the basis of their historical value and applicability (hypothetical use, correct use) to the clinical setting. At present, it is possible to assert that: a) exogenous albumin is not an ideal colloid; b) the effects on plasma volume expansion are not entirely predictable, especially in pathologic states accompanied by leaky capillary membranes; c) albumin supplementation shows no benefit on many kinds of tissue edema; d) the supplementation of albumin has no influence on outcome. It is possible to demonstrate the role of albumin as a substance with unique properties that make it useful, but further experimental and clinical data will be necessary and represent new areas for future exploration. Given the protein's cost, the routine use of albumin does not appear to be justified, until new data indicate otherwise.

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.

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.

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.

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.

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.