Evaluation of Drug Wastage in the Operating Rooms and Intensive Care Units of a Regional Health Service.

BACKGROUND: Pharmacological treatments for critical processes in patients need to be initiated as rapidly as possible; for this reason, it is a standard of care to prepare the main anesthesia and emergency drugs in advance. As a result, 20%-50% of the prepared drugs remain unused and are then discarded. Decreasing waste by optimizing drug use is an attractive strategy for meeting both cost containment and environmental sustainability. The primary end point of this study was to measure the actual amount of drug wastage in the operating rooms (ORs) and intensive care units (ICUs) of a Regional Health Service (RHS). The secondary end point was to analyze and estimate the economic implications of this waste for the Health Service and to suggest possible measures to reduce it. METHODS: This prospective observational multicenter study was conducted across 12 hospitals, all of which belong to the same RHS in the north-east of Italy. Data collection took place in March 2018 and included patients admitted to ICUs, emergency areas, and ORs of the participating hospitals. Data concerning drug preparation and administration were collected for all consecutive patients, independent of case types and of whether operations were scheduled or unscheduled. Drug wastage was defined as follows: drugs prepared in ready-to-use syringes but not administered at all and discarded untouched. We then estimated the costs of wasted drugs for a 1-year period using the data from this study and the yearly regional pharmacy orders of drugs provided to the ORs and ICUs. We also performed a sensitivity analysis to validate the robustness of our assumptions and qualitative conclusions. RESULTS: We collected data for a total of 13,078 prepared drug syringes. Drug wastage varied from 7.8% (Urapidil, an alpha-1 antagonist antihypertensive) to 85.7% (epinephrine) of prepared syringes, with an overall mean wastage rate of 38%. The estimated yearly waste was 139,531 syringes, for a total estimated financial cost of €78,060 ($92,569), and an additional quantity of medical waste amounting to 4968 kg per year. The total provider time dedicated to the preparation of unused drugs was predicted to be 1512 working hours per year. CONCLUSIONS: The overall extent of drug wastage in ORs and ICUs is concerning. Interventions aimed at minimizing waste-related costs and improving the environmental sustainability of our practice are paramount. Effort should be put into designing a more efficient workflow that reduces this waste while providing for the emergency availability of these medications in the OR and ICU.

Intensive care unit discharge: mind the gap!

Mortality after intensive care discharge is a hot topic in critical care medicine. Many factors probably play a role: patient's comorbidities and severity of the disease may have great impact on mortality. However it should be taken into account also the level of care that characterizes the ward in which the patient is discharged to. A soft transition from intensive care units to the other hospital wards is desirable to avoid the traumatic step that the fragile post-ICU patient has to face with.

A look at the past to draw lessons for the future: how the case of an urgent ICU transfer taught us to always be ready with a plan B.

Objective: The urgent transfer of an intensive care unit (ICU) is particularly challenging because it carries a high clinical and infectious risk and is a critical node in a hospital's patient flow. In early 2017, exceptional rainfall damaged the roof of the tertiary hospital in Udine, necessitating the relocation of one of the three ICUs for six months. We decided to assess the impact of this transfer on quality of care and patient safety using a set of indicators, primarily considering the incidence of healthcare-associated infections (HAIs) and mortality rates. Methods: We performed a retrospective, observational analysis of structural, process, and outcome indicators comparing the pre- and posttransfer phases. Specifically, we analyzed data between July 2016 and June 2017 for the transferred ICU and examined mortality and the incidence of HAI. Results: Despite significant changes in structural and organizational aspects of the unit, no differences in mortality rates or cumulative incidence of HAIs were observed before/after transfer. We collected data for all 393 patients (133 women, 260 men) admitted to the ICU before (49.4%) and after transfer (50.6%). The mortality rate for 100 days in the ICU was 1.90 (34/1791) before and 2.88 (37/1258) after transfer (p = 0.063). The evaluation of the occurrence of at least one HAI included 304 patients (102 women and 202 men), as 89 of them were excluded due to a length of stay in the ICU of less than 48 h; again, there was no statistical difference between the two cumulative incidences (13.1% vs. 6.9%, p = 0.075). Conclusion: In the case studied, no adverse effects on patient outcomes were observed after urgent transfer of the injured ICU. The indicators used in this study may be an initial suggestion for further discussion.

Tocilizumab administration in COVID-19 patients: Water on the fire or gasoline?

Tocilizumab is widely being used to treat COVID-19. Although reducing systemic inflammation, it also increases the risk for secondary infections as a result of the immunosuppression produced. We report the case of a 69-year-old patient admitted to the ICU with severe respiratory distress caused by COVID-19 pneumonia who developed pulmonary aspergillosis. On the basis of these findings, we suggest early testing for pulmonary aspergillosis in COVID-19 patients treated with tocilizumab.

Learning from the Italian experience during COVID-19 pandemic waves: be prepared and mind some crucial aspects.

COVID-19 pandemic has rapidly spread worldwide causing a serious challenge to the global medical community. Italy was struck hard during the first wave earlier this year and several weaknesses as well as general unpreparedness of the national healthcare system were acknowledged. Learning essential lessons from the past, we realized how implementing contingency response measures, human resources and social dynamics could have changed the outcome if promptly adopted. This review translates the previous experience into strategic actions that has to be considered when developing appropriate national and regional operational plans to respond to a pandemic.

Prehospital Emergency Medical Services: Paper Versus Technology.

Digital technology has an essential role in the development and application of innovations within the health care system. Its application is not limited to the hospital environment but extends to the emergency medical services system. The experimental phase of the shift to electronic emergency medical services documentation was performed within the Azienda Sanitaria Universitaria Friuli Centrale of Udine (Italy), a local health authority covering about 533 000 inhabitants. Considering the results of this study, we believe it is important to continue to update the methods of data collection and analysis in correlation with the management and outcomes of the patients.

Perioperative management of spinal cord injury: the anesthesiologist's point of view.

BACKGROUND: Traumatic spinal cord injury (SCI) is one of the most devastating events a person can experience. It may be life-threatening or result in long-term disability. This narrative review aims to delineate a systematic step-wise airways, breathing, circulation and disability (ABCD) approach to perioperative patient management during spinal cord surgery in order to fill some of the gaps in our current knowledge. METHODS: We performed a comprehensive review of the literature regarding the perioperative management of traumatic spinal injuries from May 15, 2020, to December 13, 2020. We consulted the PubMed and Embase database libraries. RESULTS: Videolaryngoscopy supplements the armamentarium available for airway management. Optical fiberscope use should be evaluated when intubating awake patients. Respiratory complications are frequent in the acute phase of traumatic spinal injury, with an estimated incidence of 36-83%. Early tracheostomy can be considered for expected difficult weaning from mechanical ventilation. Careful intraoperative management of administered fluids should be pursued to avoid complications from volume overload. Neuromonitoring requires investments in staff training and cooperation, but better outcomes have been obtained in centers where it is routinely applied. The prone position can cause rare but devastating complications, such as ischemic optic neuropathy; thus, the anesthetist should take the utmost care in positioning the patient. CONCLUSIONS: A one-size fit all approach to spinal surgery patients is not applicable due to patient heterogeneity and the complexity of the procedures involved. The neurologic outcome of spinal surgery can be improved, and the incidence of complications reduced with better knowledge of patient-specific aspects and individualized perioperative management.

CORonavirus-19 mild to moderate pneumonia Management with blood Ozonization in patients with Respiratory failure (CORMOR) multicentric prospective randomized clinical trial.

BACKGROUND: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. METHODS: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). RESULTS: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. CONCLUSION: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.

Postoperative complications after minimally invasive esophagectomy in the prone position: any anesthesia-related factor?

OBJECTIVE: To evaluate the incidence of postoperative complications arising within 30 days of minimally invasive esophagectomy in the prone position with total lung ventilation and their relationship with 30-day and 1-year mortality. Secondary outcomes included possible anesthesia-related factors linked to the development of complications. METHODS: The study is a retrospective single-center observational study at the Anesthesia and Surgical Department of a tertiary care center in the northeast of Italy. Patients underwent cancer resection through esophagectomy in the prone position without one-lung ventilation. RESULTS: We included 110 patients from January 2010 to December 2017. A total of 54% of patients developed postoperative complications that increased mortality risk at 1 year of follow-up. Complications postponed first oral intake and delayed patient discharge to home. Positive intraoperative fluid balance was related to increased mortality and the risk to develop postoperative complications. C-reactive protein at third postoperative day may help detect complication onset. CONCLUSIONS: Complication onset has a great impact on mortality after esophagectomy. Some anesthesia-related factors, mainly fluid balance, may be associated with postoperative mortality and morbidity. These factors should be carefully taken into account to obtain better outcomes after esophagectomy in the prone position without one-lung ventilation.

Blood ozonization in patients with mild to moderate COVID-19 pneumonia: a single centre experience.

The emerging outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. We prescribed some promising medication to our patients with mild to moderate pneumonia due to SARS-CoV-2, however such drugs as chloroquine, hydrossichloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab) were not confirmed as effective against SARS-CoV2. We, therefore, started to use auto-hemotherapy treated with an oxygen/ozone (O2/O3) gaseous mixture as adjuvant therapy. In Udine University Hospital (Italy) we performed a case-control study involving hospitalized adult patients with confirmed COVID-19 with mild to moderate pneumonia. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU-Società Italiana di Medicina di Emergenza-Urgenza) and patients that met criteria of phenotypes 2 to 4 were treated with best available therapy (BAT), with or without O3-autohemotherapy. 60 patients were enrolled in the study: 30 patients treated with BAT and O2/O3 mixture, as adjuvant therapy and 30 controls treated with BAT only. In the group treated with O3-autohemotherapy plus BAT, patients were younger but with more severe clinical phenotypes. A decrease of SIMEU clinical phenotypes was observed (2.70 ± 0.67 vs. 2.35 ± 0.88, p = 0.002) in all patients during hospitalization but this clinical improvement was statistically significant only in O3-treated patients (2.87 ± 0.78 vs. 2.27 ± 0.83, p < 0.001), differently to the control group (2.53 ± 0.51 vs. 2.43 ± 0.93, p = 0.522). No adverse events were observed associated with the application of O2/O3 gaseous mixture. O2/O3 therapy as adjuvant therapy could be useful in mild to moderate pneumonia due to SARS-CoV-2. Randomized prospective study is ongoing [Clinical Trials.gov ID: Z7C2CA5837].

Introducing Broselow colour coded system for paediatric emergency management in a non paediatric general hospital.

Paediatric emergency management is a very stressful clinical event especially when it occurs in a non paediatric hospital. Low self confidence, non familiarity with drug dosages and proper equipment selection are the main cause of professional insecurity. In this paper, after a short review dealing with main differences between child and adult patient, we consider the advantages offered by Broselow method approach to paediatric emergences. Finally we describe the strategy we followed to introduce Broselow method in our Institution.

Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care.

OBJECTIVE: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. METHODS: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). RESULTS: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. CONCLUSION: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.

Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the hypothesis that an adjunctive therapy with methylprednisolone and unfractionated heparin (UFH) or with methylprednisolone and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill ventilated patients with pneumonia from SARS-CoV-2 infection compared to LMWH alone. TRIAL DESIGN: The study is designed as a multi-centre, interventional, parallel group, superiority, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned to one of the three treatment groups in a ratio 1:1:1. PARTICIPANTS: Inpatients will be recruited from 8 Italian Academic and non-Academic Intensive Care Units INCLUSION CRITERIA (ALL REQUIRED): 1. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 2. Positive pressure ventilation (either non-invasive or invasive) from > 24 hours 3. Invasive mechanical ventilation from < 96 hours 4. PaO2/FiO2 ratio lower than 150 mmHg 5. D-dimer level > 6 times the upper limit of normal reference range 6. C-reactive Protein > 6-fold upper the limit of normal reference range EXCLUSION CRITERIA: 1. Age < 18 years 2. On-going treatment with anticoagulant drugs 3. Platelet count < 100.000/mm3 4. History of heparin-induced thrombocytopenia 5. Allergy to sodium enoxaparin or other LMWH, UFH or methylprednisolone 6. Active bleeding or on-going clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment 7. Recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery 8. Chronic assumption or oral corticosteroids 9. Pregnancy or breastfeeding or positive pregnancy test. In childbearing age women, before inclusion, a pregnancy test will be performed if not available 10. Clinical decision to withhold life-sustaining treatment or "too sick to benefit" 11. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 12. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: • LMWH group: patients in this group will be administered enoxaparin at standard prophylactic dosage. • LMWH + steroid group: patients in this group will receive enoxaparin at standard prophylactic dosage and methylprednisolone. • UFH + steroid group: patients in this group will receive UFH at therapeutic dosages and methylprednisolone. UFH will be administered intravenously in UFH + steroid group at therapeutic doses. The infusion will be started at an infusion rate of 18 UI/kg/hour and then modified to obtain aPTT Ratio in between the range of 1.5-2.0. aPTT will be periodically checked at intervals no longer than 12 hours. The treatment with UFH will be administered up to ICU discharge. After ICU discharge anticoagulant therapy may be interrupted or switched to prophylaxis with LMWH in the destination ward up to clinical judgement of the attending physician. Enoxaparin will be administered in both LMWH group and LMWH + steroid group at standard prophylactic dose (i.e., 4000 UI once day, increased to 6000 UI once day for patients weighting more than 90 kg). The treatment will be administered subcutaneously once a day up to ICU discharge. After ICU discharge it may be continued or interrupted in the destination ward up to clinical judgement of the attending physician. Methylprednisolone will be administered in both LMWH + steroid group and UHF + steroid group intravenously with an initial bolus of 0,5 mg/kg followed by administration of 0,5 mg/kg 4 times daily for 7 days, 0,5 mg/kg 3 times daily from day 8 to day 10, 0,5 mg/kg 2 times daily at days 11 and 12 and 0,5 mg/kg once daily at days 13 and 14. MAIN OUTCOMES: Primary Efficacy Endpoint: All-cause mortality at day 28 Secondary Efficacy Endpoints: - Ventilation free days (VFDs) at day 28, defined as the total number of days that patient is alive and free of ventilation (either invasive or non-invasive) between randomization and day 28 (censored at hospital discharge). - Need of rescue administration of high-dose steroids or immune-modulatory drugs; - Occurrence of switch from non-invasive to invasive mechanical ventilation during ICU stay; - Delay from start of non-invasive ventilation to switch to invasive ventilation; - All-cause mortality at ICU discharge and hospital discharge; - ICU free days (IFDs) at day 28, defined as the total number of days between ICU discharge and day 28. - Occurrence of new infections from randomization to day 28; including infections by Candida, Aspergillus, Adenovirus, Herpes Virus e Cytomegalovirus - Occurrence of new organ dysfunction and grade of dysfunction during ICU stay. - Objectively confirmed venous thromboembolism, stroke or myocardial infarction; Safety endpoints: - Occurrence of major bleeding, defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); - Occurrence of clinically relevant non-major bleeding, defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug. RANDOMIZATION: A block randomisation will be used with variable block sizes (block size 4-6-8), stratified by 3 factors: Centre, BMI (<30/≥30) and Age (<75/≥75). Central randomisation will be performed using a secure, web-based, randomisation system with an allocation ratio of 1:1:1. The allocation sequence will be generated by the study statistician using computer generated random numbers. BLINDING (MASKING): Participants to the study will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that the combined use of UHF and steroid versus the LMWH group will significantly reduce the risk of death at day 28. The overall sample size in this study is expected to be 210 with a randomization 1:1:1 and seventy patients in each group. Assuming an alpha of 2.5% (two tailed) and mortality rate in LMWH group of 50%, as indicated from initial studies of ICU patients, the study will have an 80% power to detect at least a 25 % absolute reduction in the risk of death between: a) LMHW + steroid group and LMWH group or b) UHF + steroid group and LMWH group. The study has not been sized to assess the difference between LMHW + steroid group and UHF + steroid group, therefore the results obtained from this comparison will need to be interpreted with caution and will need further adequately sized studies confirm the effect. On the basis of a conservative estimation, that 8 participating sites admit an average of 3 eligible patients per month per centre (24 patients/month). Assuming that 80 % of eligible patients are enrolled, recruitment of 210 participants will be completed in approximately 10 months. TRIAL STATUS: Protocol version 1.1 of April 26th, 2020. Recruitment start (expected): September 1st, 2020 Recruitment finish (expected): June 30th, 2021 TRIAL REGISTRATION: EudraCT number 2020-001921-30 , registered on April 15th, 2020 AIFA approval on May 4th, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

A five-year retrospective study of out-of-hospital cardiac arrest in a north-east Italian urban area.

BACKGROUND: The reporting and analysing of data of out-of-hospital cardiac arrests encourages the quality improvement of the emergency medical services. For this reason, the establishment of a sufficiently large patient database is intended to allow analysis of resuscitation treatments for out-of-hospital cardiac arrests and performances of different emergency medical services. AIMS: The aim of this study was to describe the demographics, characteristics, outcomes and determinant factors of survival for patients who suffered an out-of-hospital cardiac arrest. METHODS: this was a retrospective study including all out-of-hospital cardiac arrest cases treated by the emergency medical service in the district of Udine (Italy) from 1 January 2010-31 December 2014. RESULTS: A total of 1105 out-of-hospital cardiac arrest patients were attended by the emergency medical service. Of these, 489 (44.2%) underwent cardiopulmonary resuscitation, and return of spontaneous circulation was achieved in 142 patients (29%). There was a male predominance overall, and the main age was 72.6 years (standard deviation 17.9). Cardiopulmonary resuscitation before emergency medical service arrival was performed on 62 cases (44%) in the return of spontaneous circulation group, and on 115 cases (33%) in the no return of spontaneous circulation group ( p<0.024). Among the 142 cases of return of spontaneous circulation, 29 (5.9%) survived to hospital discharge. There was a smaller likelihood of return of spontaneous circulation when patients were female (odds ratio 0.61, 0.40-0.93). Patients who had an out-of-hospital cardiac arrest with an initial shockable rhythm (odds ratio 6.33, 3.86-10.39) or an age <60 years (odds ratio 2.91, 1.86-4.57) had a greater likelihood of return of spontaneous circulation. In addition, bystander cardiopulmonary resuscitation (odds ratio 1.56, 1.04-2.33) was associated with an increased chance of return of spontaneous circulation. CONCLUSION: The incidence of out-of-hospital cardiac arrest and survival rate lies within the known range. A wider database is necessary to achieve a better knowledge of out-of-hospital cardiac arrest and to drive future investments in the healthcare system.

Effect of Protein-Fortified Diet on Nitrogen Balance in Critically Ill Patients: Results from the OPINiB Trial.

Nitrogen balance (NB) is considered a good marker of adequate protein intake and it has been suggested to be a good predictor of patients' health outcomes. However, in literature, there is a lack of large randomized trials examining NB-guided protein intake in patients in intensive care units (ICUs). A randomized controlled trial enrolling patients admitted to ICU was done to compare changes in NB. Participants were randomized to a standard or protein-fortified diet (protein intake of 1.8 g/kg/day according to the guidelines of the Society of Critical Care Medicine and the American Society for Parenteral and Enteral Nutrition). The primary endpoint was represented by the NB on Day 1, 3, and study exit. Forty patients were enrolled in the study (19 in the protein-fortified group). The longitudinal analysis showed that, on Day 3, patients randomized to the protein-fortified diet were more likely (p < 0.001) to present better NB (at 3 days, patients in the protein-fortified diet were estimated to have a nitrate value of 5.22 g more than patients in the standard diet, 95% CI 3.86-6.58). The protein-fortified diet was found to be significantly and directly associated with changes in NB in critically ill patients admitted to ICU.

Persistent hypoxemia after an asthma attack.

The presence of an unknown intracardiac shunt due to a patent foramen ovale may be an unusual cause of hypoxemia. We report the case of a patient who presented persistent hypoxemia after an adequate treatment for a severe asthma attack requiring intensive care unit admission. The patient underwent a transthoracic microbubbles contrast echocardiography that showed a massive patent foramen ovale. The favorable clinical course and the absence of major signs and symptoms related to patent foramen ovale allowed a conservative approach with a follow-up program. Patent foramen ovale should be suspected in case of persistent hypoxemia after a severe asthma attack had resolved.

Optimizing Protein Intake and Nitrogen Balance (OPINiB) in Adult Critically Ill Patients: A Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Adequate nutrition of critically ill patients plays a key role in the modulation of metabolic response to stress. OBJECTIVE: This paper presents the development of a protocol for a randomized controlled trial (RCT) aimed at comparing clinical outcomes of patients in the intensive care unit (ICU) administered with standard and protein-fortified diet. Together with the RCT study protocol, the results of the observational analysis conducted to assess the feasibility of the RCT are presented. METHODS: An RCT on adult patients admitted to ICU and undergoing mechanical ventilation in the absence of renal or hepatic failure will be conducted. Patients enrolled will be randomized with an allocation rate of 1:1 at standard diet versus protein-fortified diet. The estimated sample size is 19 per arm, for a total of 38 patients to be randomized. RESULTS: Enrollment began in January 2017. In the feasibility study, 14 patients were enrolled. Protein administration increased significantly (P<.001) over time but was significantly lower compared to that recommended (P<.001). Blood urea nitrogen significantly increased (P<.03) over the period of observation. Such increased catabolism resulted in negative cumulative nitrogen balance (NB) in all patients, and some patients presented with a more negative NB compared to the others. CONCLUSIONS: Results of the feasibility study clearly confirmed that protein provision in ICU patients is below that recommended and that this results in impaired NB. The emerging of an interindividual variability in NB will be further analyzed in the RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT02990065; https://clinicaltrials.gov/ct2/show/NCT02990065 (Archived by WebCite at http://www.webcitation.org/6prsqZdRM).