Guidelines for inhaled sedation in the ICU.

INTRODUCTION AND OBJECTIVES: Sedation is used in intensive care units (ICU) to improve comfort and tolerance during mechanical ventilation, invasive interventions, and nursing care. In recent years, the use of inhalation anaesthetics for this purpose has increased. Our objective was to obtain and summarise the best evidence on inhaled sedation in adult patients in the ICU, and use this to help physicians choose the most appropriate approach in terms of the impact of sedation on clinical outcomes and the risk-benefit of the chosen strategy. METHODOLOGY: Given the overall lack of literature and scientific evidence on various aspects of inhaled sedation in the ICU, we decided to use a Delphi method to achieve consensus among a group of 17 expert panellists. The processes was conducted over a 12-month period between 2022 and 2023, and followed the recommendations of the CREDES guidelines. RESULTS: The results of the Delphi survey form the basis of these 39 recommendations - 23 with a strong consensus and 15 with a weak consensus. CONCLUSION: The use of inhaled sedation in the ICU is a reliable and appropriate option in a wide variety of clinical scenarios. However, there are numerous aspects of the technique that require further study.

Vitamin C and thiamine for the treatment of refractory septic shock in surgical critically ill patients: a retrospective before-and-after study.

OBJECTIVE: This study aimed to evaluate whether early vitamin C and thiamine administration was associated with a lower 28-day and in-hospital mortality in surgical critically ill patients with refractory septic shock. METHODS: We performed a retrospective before-and-after study on patients with refractory septic shock. According to local protocol, hydrocortisone is initiated in case of refractory septic shock. In January 2017, the protocol was changed and vitamin C and thiamine were included. Patients who were admitted in 2015-2016 and 2017-2018 were included in the control and treatment groups, respectively. The primary end point was 28-day and in-hospital mortality. Secondary end points were ICU mortality, ICU and hospital length of stay, duration of vasopressors and mechanical ventilation, use of renal replacement therapy (RRT), and the modification in serum procalcitonin and SOFA score during the first 72 h. RESULTS: A total of 120 patients were included (58 in the treatment group and 62 in the control group). Log-rank test in Kaplan-Meier curves showed lower 28-day and in-hospital mortality over time in the treatment group (p=0.021 and p=0.035, respectively) but it not reached statistical significance in ICU mortality over time (p=0.100). The need of RRT was less frequent in treatment group (17.2% vs. 37.1%, p=0.024). There were no differences in other secondary outcomes. CONCLUSIONS: Intravenous vitamin C and thiamine administration in surgical patients with refractory septic shock may be associated with a lower 28-day and in-hospital mortality. Further prospective studies are needed in refractory septic shock.

Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial.

INTRODUCTION: Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation. METHODS AND ANALYSIS: The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage. ETHICS AND DISSEMINATION: The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research. TRIAL REGISTRATION NUMBER: NCT04647396.

The role of cefiderocol in clinical practice.

Cefiderocol is a new antimicrobial with a chemical structure similar to ceftazidime and cefepime. In this review we will focus on the role of cefiderocol in different clinical scenarios produced by resistant Gram-negative microorganisms, especially to carbapenems. In infections caused by Gram-negative microorganisms, inappropriate antibiotic treatment increased the risk of mortality almost fourfold. In patients with hospital-acquired infection and septic shock; with sepsis and poor functional reserve due to fragility; in immunocompromised patients; and in those with local ecology, individual history of colonization or previous infection and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) such as the presence of chronic multi-morbidities, the best option would be to start an active empirical treatment against gram-negative bacteria resistant to carbapenems and later in 24-36 h with the information obtained from the cultures we could decide on a definitive empirical or directed treatment and avoid unnecessary overuse of these antibiotics. Cefiderocol would be in these cases a good candidate due to its excellent in vitro activity against all classes of beta-lactamase-producing Gram-negatives (including carbapenemase class A, B and D producers), as well as against non-fermenting Gram-negatives such as P. aeruginosa, Acinetobacter spp. and S. maltophilia. It is necessary to optimize the use of new antibiotics such as cefiderocol, guaranteeing the best available treatment to patients while delaying the emergence and spread of resistance.

Controversies in the management of ESBL-producing Enterabacterales. Clinical Implications.

Extended-spectrum ß-lactamases (ESBL)-producing organisms currently represent a major health problem. Although recently published guidelines still consider carbapenems as the treatment of choice for ESBL-producing infections, it is necessary to find non-carbapenem ß-lactams as alternatives to reduce the effects associated with their overutilization. In this review we focus on these alternatives to carbepenem use. It is possible that piperacillin-tazobactam may be an alternative in clinical settings with "low inoculum" infections like urinary tract infections. Newer ß-lactam-ß-lactamase inhibitors (BLBLIs) are potential options too. The current available data support the efficacy of both ceftazidime-avibactam and ceftolozane-tazobactam against susceptible ESBL-producing Enterobacterales (ESBL-E). We are waiting for the results of MERINO-3 study to confirm whether ceftolozane-tazobactam is a good option versus meropenem for treating bloodstream infections caused by ESBL- or AmpC-producing Enterobacterales.

Secondary infections in mechanically ventilated patients with COVID-19: An overlooked matter?

OBJECTIVE: The susceptibility to infection probably increases in COVID-19 patients due to a combination of virusand drug-induced immunosuppression. The reported rate of secondary infections was quite low in previous studies. The objectives of our study were to investigate the rate of secondary infections, risk factors for secondary infections and risk factors for mortality in COVID-19 critically ill patients. METHODS: We performed a single-center retrospective study in mechanically ventilated critically ill COVID-19 patients admitted to our Critical Care Unit (CCU). We recorded the patients' demographic data; clinical data; microbiology data and incidence of secondary infection during CCU stay, including ventilator-associated pneumonia (VAP) and nosocomial bacteremia (primary and secondary). RESULTS: A total of 107 patients with a mean age 62.2 ± 10.6 years were included. Incidence of secondary infection during CCU stay was 43.0% (46 patients), including nosocomial bacteremia (34 patients) and VAP (35 patients). Age was related to development of secondary infection (65.2 ± 7.3 vs. 59.9 ± 12.2 years, p=0.007). Age ≥ 65 years and secondary infection were independent predictors of mortality (OR=2.692, 95% CI 1.068-6.782, p<0.036; and OR=3.658, 95% CI 1.385- 9.660, p=0.009, respectively). The hazard ratio for death within 90 days in the ≥ 65 years group and in patients infected by antimicrobial resistant pathogens was 1.901 (95% CI 1.198- 3.018; p= 0.005 by log-rank test) and 1.787 (95% CI 1.023-3.122; p= 0.036 by log-rank test), respectively. CONCLUSIONS: Our data suggest that the incidence of secondary infection and infection by antimicrobial resistant pathogens is very high in critically ill patients with COVID-19 with a significant impact on prognosis.

Practical recommendations for the perioperative management of the patient with suspection or serious infection by coronavirus SARS-CoV. / Recomendaciones prácticas para el manejo perioperatorio del paciente con sospecha o infección grave por coronavirus SARS-CoV-2.

In December 2019, the Wuhan Municipal Health and health Commission (Hubei Province, China) reported a series of cases of pneumonia of unknown etiology. On January 7, 2020, the Chinese authorities identified as a causative agent of the outbreak a new type of virus of the Coronaviridiae family, called SARS-CoV-2. Since then, thounsands of cases have been reported with global dissemination. Infections in humans cause a broad clinical spectrum ranging from mild upper respiratory tract infection, to severe acute respiratory distress syndrome and sepsis. There is not specific treatment for SARS-CoV-2, which is why the fundamental aspects are to establish adequate prevention measures and support treatment and management of complications.

Prognosis and predictors of mortality in critically ill elderly patients. / Pronóstico y predictores de mortalidad de los pacientes ancianos críticos.

OBJECTIVES: to evaluate mortality of patients≥80 years admitted to the Surgical Intensive Care Unit (SICU), global hospital mortality and factors related to it. MATERIAL AND METHODS: observational retrospective study of patients≥80 years admitted to SICU between June 2012 and June 2015. RESULTS: a total of 299 patients were included, 54 of them died in the SICU (18.1%) and 80 patients (26.8%) died during their hospital stay. SICU mortality was independently related to age (OR=1.125; 95%CI: 1.042-1.215; P=.003), SAPS II (OR=1.026; 95% CI: 1.008-1.044; P=.004), need for renal replacement therapy (RRT) (OR=1.960; 95%CI: 1.046-3.671; P=.036) and need for mechanical ventilation for more than 24hours (OR=2.834; 95%CI: 1.244-6.456; P=.013). Factors independently related to hospital mortality were age (OR=1.125; 95%CI: 1.054-1.192; P<.001), SOFA score (OR=1.154; 95% CI: 1.079-1.235; P<.001), need for RRT (OR=1.924; 95%CI: 1.121-3.302; p=0.018) and need for mechanical ventilation for more than 24hours (OR=3.144; 95% CI: 1.771-5.584; P<.001). CONCLUSIONS: In critically ill patients over 80 years hospital mortality was independently related to age, SOFA score, RRT need and need for mechanical ventilation for more than 24hours. Our results raise important issues about end-of-life care and life-sustaining interventions in elderly, critically ill patients.

Current aspects in sepsis approach. Turning things around.

The incidence and prevalence of sepsis depend on the definitions and records that we use and we may be underestimating their impact. Up to 60% of the cases come from the community and in 30-60% we obtain microbiological information. Sometimes its presentation is ambiguous and there may be a delay in its detection, especially in the fragile population. Procalcitonin is the most validated biomarker for bacterial sepsis and the one that best discriminates the non-infectious cause. Presepsin and pro-adrenomedullin are useful for early diagnosis, risk stratification and prognosis in septic patients. The combination of biomarkers is even more useful to clarify an infectious cause than any isolated biomarker. Resuscitation with artificial colloids has worse results than crystalloids, especially in patients with renal insufficiency. The combination of saline solution and balanced crystalloids is associated with a better prognosis. Albumin is only recommended in patients who require a large volume of fluids. The modern molecular methods on the direct sample or the identification by MALDI-TOF on positive blood culture have helped to shorten the response times in diagnosis, to optimize the antibiotic treatment and to facilitate stewardship programs. The hemodynamic response in neonates and children is different from that in adults. In neonatal sepsis, persistent pulmonary hypertension leads to an increase in right ventricular afterload and heart failure with hepatomegaly. Hypotension, poor cardiac output with elevated systemic vascular resistance (cold shock) is often a terminal sign in septic shock. Developing ultra-fast Point-of-Care tests (less than 30 minutes), implementing technologies based on omics, big data or massive sequencing or restoring "healthy" microbiomes in critical patients after treatment are the main focuses of research in sepsis. The main benefits of establishing a sepsis code are to decrease the time to achieve diagnosis and treatment, improve organization, unify criteria, promote teamwork to achieve common goals, increase participation, motivation and satisfaction among team members, and reduce costs.

Severe cefepime-induced status epilepticus treated with haemofiltration.

Neurotoxicity caused by cefepime may occur predominantly in patients with impaired renal function. A case of a cefepime-induced non-convulsive status epilepticus (NCSE) is presented. A 65-year-old woman suffered a severe NCSE due to cefepime in the presence of acute renal failure, requiring coma induction with sodium thiopental. A serious interaction between valproic acid (VPA) and meropenem was also produced after changing cefepime to meropenem. Continuous veno-venous haemofiltration was employed to improve cefepime clearance, and the patient progressively regained her previous mental condition. In conclusion, the cefepime dose must be adjusted according to renal function in order to avoid toxicity in patients with renal failure. Electroencephalogram should be considered in cases of acute confusional state in patients receiving cefepime, to achieve early detection of NCSE. Continuous renal replacement therapy may be successfully employed in severe cases in order to accelerate cefepime removal. Likewise, meropenem should not be used concomitantly with VPA.

Spanish survey on enhanced recovery after surgery. / Encuesta nacional sobre cirugía con recuperación intensificada.

INTRODUCTION: The aim of this study was to determine the interest in ERAS protocols, and the extent to which clinicians are familiar with and apply these protocols during perioperative care. MATERIALS AND METHODS: Free access survey hosted on the Spanish Society of Anesthesiology and Critical Care; Spanish Association of Surgeons and Spanish Society of Enteral and Parenteral nutrition and ERAS Spain (GERM) websites conducted between September and December 2014. RESULTS: The survey was answered by 272 professionals (44.5% anaesthetists, 45.2% general surgeons) from 110 hospitals, 73% of whom had experience in ERAS protocols. Most (86.1%) had specific knowledge of ERAS protocols, whereas only 50.9% were familiar with ERAS recommendations and 42.4% with GERM recommendations. Most (73.1%) respondents reported that ERAS protocols are performed in their hospitals, mainly in colorectal surgery (93%), and 52.2% reported that GERM/ERAS recommendations are followed. Nearly all (95.5%) would be interested in the development of multidisciplinary national guidelines. Less than half (46.6%) perform preoperative nutritional assessment, albeit without a universal malnutrition screening method (56.8%). Preoperative loading with carbohydrate drinks is carried out in only 51.4% of cases; nasogastric tube and drainage are avoided (79.3%), prophylaxis for postoperative nausea and vomiting (73.4%), goal directed fluid therapy (73.3%), and active normothermia maintenance (87.4%) are performed. In most cases, mobilization (90.1%) and early feeding (87.9%) are performed. The leading causes of protocol failure are postoperative nausea and vomiting (46.5%) and ileus (58.9%). CONCLUSION: Clinicians in Spain are familiar with fast track protocols, although there is no overall consensus, and hospitals do not adhere to existing guidelines. Overall compliance with the items of the protocol is adequate, although perioperative nutritional management is poor.