Epidemiology, ventilation management and outcome in patients receiving intensive care after non-thoracic surgery - Insights from the LAS VEGAS study.

INTRODUCTION AND OBJECTIVES: Information about epidemiology, ventilation management and outcome in postoperative intensive care unit (ICU) patients remains scarce. The objective was to test whether postoperative ventilation differs from that in the operation room. MATERIAL AND METHODS: This was a substudy of the worldwide observational LAS VEGAS study, including patients undergoing non-thoracic surgeries. Of 146 study sites participating in the LAS VEGAS study, 117 (80%) sites reported on the postoperative ICU course, including ventilation and complications. The coprimary outcomes were two key elements of ventilator management, i.e., tidal volume (VT) and positive end-expiratory pressure (PEEP). Secondary outcomes included the proportion of patients receiving low VT ventilation (LTVV, defined as ventilation with a median VT < 8.0 ml/kg PBW), and the proportion of patients developing postoperative pulmonary complications (PPC), including ARDS, pneumothorax, pneumonia and need for escalation of ventilatory support, ICU and hospital length of stay, and mortality at day 28. RESULTS: Of 653 patients who were admitted to the ICU after surgery, 274 (42%) patients received invasive postoperative ventilation. Median postoperative VT was 8.4 [7.3-9.8] ml/kg predicted body weight (PBW), PEEP was 5 [5-5] cm H2O, statistically significant but not meaningfully different from median intraoperative VT (8.1 [7.3-8.9] ml/kg PBW; P < 0.001) and PEEP (4 [2-5] cm H2O; P < 0.001). The proportion of patients receiving LTVV after surgery was 41%. The PPC rate was 10%. Length of stay in ICU and hospital was independent of development of a PPC, but hospital mortality was higher in patients who developed a PPC (24 versus 4%; P < 0.001). CONCLUSIONS: In this observational study of patients undergoing non-thoracic surgeries, postoperative ventilation was not meaningfully different from that in the operating room. Like in the operating room, there is room for improved use of LTVV. Development of PPC is associated with mortality.

Association between intra-operative cardiac arrest and country Human Development Index status: a systematic review with meta-regression analysis and meta-analysis of observational studies.

Intra-operative cardiac arrests differ from most in-hospital cardiac arrests because they reflect not only the patient's condition but also the quality of surgery and anaesthesia care provided. We assessed the relationship between intra-operative cardiac arrest rates and country Human Development Index (HDI), and the changes occurring in these rates over time. We searched PubMed, EMBASE, Scopus, LILACS, Web of Science, CINAHL and SciELO from inception to 29 January 2020. For the global population, rates of intra-operative cardiac arrest and baseline ASA physical status were extracted. Intra-operative cardiac arrest rates were analysed by time, country HDI status and ASA physical status using meta-regression analysis. Proportional meta-analysis was performed to compare intra-operative cardiac arrest rates and ASA physical status in low- vs. high-HDI countries and in two time periods. Eighty-two studies from 25 countries with more than 29 million anaesthetic procedures were included. Intra-operative cardiac arrest rates were inversely correlated with country HDI (p = 0.0001); they decreased over time only in high-HDI countries (p = 0.040) and increased with increasing ASA physical status (p < 0.0001). Baseline ASA physical status did not change in high-HDI countries (p = 0.106), while it decreased over time in low-HDI countries (p = 0.040). In high-HDI countries, intra-operative cardiac arrest rates (per 10,000 anaesthetic procedures) decreased from 9.59 (95%CI 6.59-13.16) pre-1990 to 5.17 (95%CI 4.42-5.97) in 1990-2020 (p = 0.013). During the same time periods, no improvement was observed in the intra-operative cardiac arrest rates in low-HDI countries (p = 0.498). Odds ratios of intra-operative cardiac arrest rates in ASA 3-5 patients were 8.48 (95%CI 1.67-42.99) times higher in low-HDI countries than in high-HDI countries (p = 0.0098). Intra-operative cardiac arrest rates are related to country-HDI and decreased over time only in high-HDI countries. The widening gap in these rates between low- and high-HDI countries needs to be addressed globally.

Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review.

BACKGROUND: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. RESULTS: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. CONCLUSIONS: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.

Mediastinitis in the intensive care unit patient: a narrative review.

BACKGROUND: Mediastinitis is a rare but severe infection, defined as an inflammation of the connective tissues and structures within the mediastinum. Due to its proximity to vital structures, mediastinitis represents a highly morbid pathological process associated with a high risk of mortality. In most cases mediastinitis requires treatment in the intensive care unit. OBJECTIVES: To highlight to the reader the clinical features of mediastinitis, to attempt to define each clinical scenario, to describe the responsible pathogens and finally to depict both the medical and surgical treatments. SOURCES: We performed a literature search of the PubMed and Cochrane libraries, limited for articles published between January 2003 and December 2018, reporting on acute mediastinitis. CONTENT: The term covers different entities of different aetiologies including deep sternal wound infection related to sternotomy; oesophageal perforation or anastomosis leakage; and finally descending necrotizing mediastinitis, often secondary to oropharyngeal abscess. The responsible pathogens and therefore subsequent management depends on the underlying aetiology. Empirical antimicrobial therapy should cover the suspected microorganisms while surgery and supportive measures should aim to reduce the inoculum of pathogens by providing adequate drainage and debridement. IMPLICATIONS: Literature concerning mediastinitis in the intensive care unit is relatively scarce. We have collated the evidence and reviewed the different causes and treatment options of acute mediastinitis with a particular focus on microbiological epidemiology. Future research in larger cohorts is needed to better understand the treatment of this difficult disease.

Pitfalls to avoid in the medical management of mass casualty incidents following terrorist bombings: the hospital perspective.

BACKGROUND: The unique patterns of injury following explosions together with the involvement of numerous physicians, most of whom are not experienced in trauma, may create problems in the medical management of mass casualty incidents. METHODS: Four hundred patient files admitted in 19 mass casualty events following bombing incidents were reviewed and possible areas which could impact survival were defined. RESULTS: Forty-nine (9.3 %) patients had an Injury Severity Score ≥16. Of 205 patients in whom triage decisions were available, 5 of 25 severely injured patients were undertriaged by the triage officers at the door of the hospital. Following primary evaluation inside the emergency department critical injuries in two patients were missed due to distracting, less serious injuries. Of 68 (16.1 %) patients who were operated, 28 were in need of either immediate, urgent or high-priority operations. Except for neurosurgical cases which needed to be transferred to other hospitals, there was no delay in surgery. One patient underwent negative laparotomy. There were 15 in-hospital deaths, 6 of which were deemed as either anticipated or unanticipated mortality with possibility for improvement. CONCLUSION: Medical management should be evaluated following MCIs as this may illustrate possible problems which many need to be addressed in contingency planning.

Outcomes of prospectively-collected consecutive cases of antenatal-suspected placenta accreta.

BACKGROUND: Accurate diagnosis of placenta accreta is tentative before surgery. This study developed a predictive score for antenatal diagnosis of placenta accreta through mathematical modeling using clinical signs. METHODS: Antenatal cases of suspected placenta accreta were collected prospectively in a single-site tertiary delivery center. Women with clinical signs of placenta accreta (placenta previa, number of previous cesarean deliveries and/or ultrasound suspicion of placenta accreta) were included. The diagnosis of accreta was confirmed surgically. The primary endpoint was the proportion of surgically-diagnosed placenta accreta among all suspected cases. Logistic regression modeling was performed to assess preoperative risk factors for placenta accreta. The risk score was tested on a receiver operator characteristic curve to identify subjects with placenta accreta and the optimum cut-point was chosen. RESULTS: Over nine years, 92 suspected accreta cases were identified from 46623 deliveries (0.2%). The diagnosis was confirmed at surgery in 52/92 cases (56%) and there were no maternal deaths. Blood transfusion requirements were greater in patients with placenta accreta versus patients without placenta accreta (median 7 [range 0-25, interquartile range 3-10] versus 0 [0-6, 0-2] units of blood, P <0.0001). Area under the curve of the receiver operator characteristic curve was 0.846, with contribution from three variables (placenta previa, number of previous cesarean deliveries and ultrasound suspicion), each with a P value <0.05. From the ROC curve a cut-point with 100% sensitivity and specificity 25% (95% CI 12.69%-41.20%) was achieved, compared with 86.6% sensitivity (95% CI 74.21%-94.41%) and 60.0% specificity (95% CI 43.33%-75.14%) using ultrasound alone. CONCLUSIONS: Combining diagnostic features associated with placenta accreta through mathematical modeling has better positive predictive value than ultrasound alone.

Microcalcifications increase coronary vulnerable plaque rupture potential: a patient-based micro-CT fluid-structure interaction study.

Asymptomatic vulnerable plaques (VP) in coronary arteries accounts for significant level of morbidity. Their main risk is associated with their rupture which may prompt fatal heart attacks and strokes. The role of microcalcifications (micro-Ca), embedded in the VP fibrous cap, in the plaque rupture mechanics has been recently established. However, their diminutive size offers a major challenge for studying the VP rupture biomechanics on a patient specific basis. In this study, a highly detailed model was reconstructed from a post-mortem coronary specimen of a patient with observed VP, using high resolution micro-CT which captured the microcalcifications embedded in the fibrous cap. Fluid-structure interaction (FSI) simulations were conducted in the reconstructed model to examine the combined effects of micro-Ca, flow phase lag and plaque material properties on plaque burden and vulnerability. This dynamic fibrous cap stress mapping elucidates the contribution of micro-Ca and flow phase lag VP vulnerability independently. Micro-Ca embedded in the fibrous cap produced increased stresses predicted by previously published analytical model, and corroborated our previous studies. The 'micro-CT to FSI' methodology may offer better diagnostic tools for clinicians, while reducing morbidity and mortality rates for patients with vulnerable plaques and ameliorating the ensuing healthcare costs.

Perioperative anaesthetic management of high-order repeat caesarean section: audit of practice in a university-affiliated medical centre.

BACKGROUND: High-order (five or more) repeat caesarean sections (HORCS) are associated with increased rates of placenta praevia, placenta accreta and peripartum hysterectomy and prolonged surgical time secondary to intra-abdominal adhesions. This study summarizes our experience in the anaesthetic management of HORCS. METHODS: The files of all parturients undergoing HORCS between January 1995 and August 2007 were reviewed to determine surgical times, rates and causes of conversion from neuraxial to general anaesthesia and the need to supplement neuraxial anaesthesia with intravenous sedation. RESULTS: Parturients (n=108) were 35+/-4.5 years old with a gestational age of 37.5+/-1.5 weeks, weighed 88+/-20 kg and had undergone 6+/-1 caesarean sections. Eighty-six (80%) were elective. Initial anaesthetic techniques included spinal (n=80, 74%), epidural (n=9, 8%), combined spinal-epidural (n=6, 6%) and general anaesthesia (n=13, 12%). Surgery lasted 38+/-19 min (median 34, range 9-120). Fourteen parturients (13%) underwent intraoperative manipulations other than caesarean section, including three hysterectomies for haemorrhage (two placenta accreta, one praevia). There were no ruptures or dehiscences of the uterine scar, intraoperative bladder/ bowel injuries or re-explorations. Apgar scores <9 at 1 (n=9, 13%) and 5 (n=6, 5%) min were related to non-anaesthetic causes. Anaesthesia was converted from neuraxial to general in five cases (5/95, 5%) but only two were due to haemorrhage. No epidural top-up doses or intravenous sedatives/analgesics were required for spinal anaesthesia. CONCLUSION: HORCS is not necessarily an indication for general anaesthesia provided uterine and placental abnormalities are sought preoperatively. In our practice single-shot spinal anaesthesia sufficed for uncomplicated HORCS.

Molecular and cellular characterization of mesenchymal progenitors for skeletal biomedical devices.

Mesenchymal cells are successfully used to create cell-loaded devices in tissue engineering. Molecular properties of the cells and interaction with polymer scaffolds regulate the development of desired tissues. The present study compared the molecular markers in mesenchymal pleuripotent C3H10T1/2 and osteogenic MBA-15 cells. The cells express transcription factors (TF) of chondro-ostegenic pathway (cbfa-1 and c-fos) and MyoD - TF of muscle differentiation pathway, but not myogenin. Analyzed cells expressed receptors for glucocorticoids, growth hormone, prolactin, and PTH, which indicates their potential responsiveness to systemic signals. Analysis of mRNA encoding for receptors of TGFbeta, TNF, and various interleukins revealed differential expression of IL-2r and TGFbeta-1r receptors, which were expressed by MBA-15 but not by C3H10T1/2 cells. Expression of functional genes indicates differences in the stages of cell differentiation: ALK was present in MBA-15 only, while both cell types expressed collagen-I. Furthermore, we evaluated the expression of adhesion proteins that mediate cell-polymer interactions by flow cytometry analysis. Cell adhesion molecules (CAMs) analyzed were integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), which have shown differential expression on cells cultured on plastic, poly(L-lactic acid) (PLLA) or poly(DL-lactide-glycolide acid) (PDLGA) polymer films. Detailed molecular characterization of mesenchymal cells will enable optimization of culture conditions for successful creation of implantable cell-loaded constructs.

Adhesion molecule expression by osteogenic cells cultured on various biodegradable scaffolds.

Design of tissue-engineered cell-loaded device involves cells seeding onto scaffolds in vitro, allowing them to settle and grow before in vivo transplantation. Interaction between scaffold and cells is important in the development of desired tissues. The present study aimed to investigate the effect of cell-polymer interactions on cell morphology and expression of surface markers of osteogenic MBA-15 cells cultured on various bioresorbable polymers. In this study, we used various polymers: poly(L-lactic acid) (PLLA), poly(DL-lactic acid) (PDLLA), poly(L-lactic-glycolic acid) (PLGA), and poly(DL-lactide-glycolide acid) PDLGA1 and PDLGA2. Expression of integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), important in cell-cell and cell-matrix interactions, were quantified by flow-cytometry analysis. Cells grown on PDLGA1 films demonstrated fivefold increase in CD62E expression and two-folds increase in CD11b expression. None of the polymers affected the levels of CD31. Identified differential effect of polymers on the expression of cell-adhesion molecules by osteoprogenitors in vitro might help to choose optimal parameters for successful engraftment of cell-loaded constructs.

Perioperative ischemia and cardiac complications in major vascular surgery: importance of the preoperative twelve-lead electrocardiogram.

PURPOSE: To investigate the associations between specific preoperative 12-lead electrocardiogram (ECG) abnormalities, perioperative ischemia, and postoperative myocardial infarction or cardiac death in major vascular surgery. METHODS: Two prospective studies on perioperative myocardial ischemia performed in two tertiary university hospitals were combined to include 405 patients. All preoperative ECGs were analyzed according to the Sokolow-Lyon criteria for left ventricular hypertrophy by investigators who were blinded to the patients' perioperative clinical course. Perioperative myocardial ischemia was detected by continuous ECG recording, and postoperative cardiac complications included myocardial infarction and cardiac death. RESULTS: A total of 19 postoperative cardiac complications occurred (two cardiac deaths and 17 myocardial infarctions). Voltage criteria for left ventricular hypertrophy (78 patients, 19%) and ST segment depression greater than 0.5 mm (98 patients, 24.2%) on preoperative ECGs were both significantly associated with postoperative myocardial infarction or cardiac death (odds ratio, 4.2 and 4.7; p = 0.001 and 0.0005, respectively) and with longer intraoperative and postoperative myocardial ischemia. In each of the two study groups, a preoperative ECG abnormality that involved voltage criteria, ST segment depression, or both (134 patients, 33.1%) was more predictive of postoperative cardiac complications than any other preoperative clinical variable, including a history of myocardial infarction or angina pectoris, diabetes mellitus, pathologic Q-wave by ECG, or preoperative myocardial ischemia. The combined duration of intraoperative and postoperative ischemia and the preoperative ECG with either voltage criteria or ST segment depression were the only independent factors associated with adverse cardiac events by multivariate analysis (p < or = 0.0001 and p = 0.02, respectively). CONCLUSION: Left ventricular hypertrophy and ST segment depression on preoperative 12-lead ECGs are important markers of increased risk for myocardial infarction or cardiac death after major vascular surgery.

The effect of colloid osmotic pressure on the survival of sheep following cardiac surgery.

The occurrence of late complications in implanted cardiac prosthetic valves has emphasized the need for the development of an animal model in which these complications are reproducible. Sheep constitute an excellent model for chronical and pathological studies of prosthetic devices. In our experience, survival of sheep following implantation of prosthetic valves is closely related to postoperative serum colloid osmotic pressure (C.O.P.). The normal range as measured in 28 healthy sheep was 16.67 +/- 0.55 mm Hg. A protocol was developed to maintain the colloid hydrostatic pressure gradient (C.H.P.G.) as close as possible to the normal physiological range, and to delay the extubation until the C.O.P. was within this range, and the C.H.P.G. greater than 7 mm Hg. Using the above protocol, a new tri-leaflet polyurethane valve was inserted into eight, five to seven month old sheep in place of the mitral and tricuspidal valves. One hour after terminating the extacorporeal circuit, the C.O.P. was measured at 13.10 +/- 0.96; but within five to six hours, it rose to 17.1 +/- 1.1. During the same period, the C.H.P.G. increased from 3.02 +/- 0.96 to 7.6 +/- 0.50 mm Hg. The postoperative period was uneventful, and all animals survived. We have thus concluded that the routine measurement and monitoring of C.O.P. constitutes a guide of great clinical importance.

Effect of experimental cardioplegia methods on normal and hypertrophied rat hearts.

The purpose of this study was to evaluate whether the addition of verapamil hydrochloride to oxygenated glucose-rich cardioplegic solution would improve myocardial preservation. The Langendorff preparation of the isolated rat heart was used. Groups of normal (WKY) and hypertrophied (SHR) hearts were treated by five different cardioplegic methods and subjected to 90 or 30 minutes of ischemia at 28 degrees to 29 degrees C and reperfusion at 37 degrees C. The following cardioplegic solutions were used: Group A, cold (16 degrees C) Krebs-Henseleit (KH) glucose free only; Group B, KH with KCL (30 mEq/L) (16 degrees C); Group C, same as B with verapamil (10 microM); Group D, perfusion with oxygenated KH solution containing KCL (30 mEq/L) for 15 minutes prior to ischemia; and Group E, same as D with verapamil (10 microM). Recovery of contraction amplitude, ischemic contracture, coronary perfusate volume, the amount of creatine kinase in the coronary perfusate, heart rate, time of revival, O2 consumption, and ischemic contracture were measured. After 30 minutes of ischemia, we did not find any significant difference among the combinations tested with respect to contraction amplitude recovery. The hearts recovered fully. After 90 minutes of ischemia, we found that the best-protected groups in the normal hearts were Groups D and E. In the hypertrophied hearts, the addition of verapamil to the enhancement solution was harmful. The use of enhancement solution without verapamil prior to ischemia provided the best myocardial protection in the hypertrophied hearts.

Haemodynamics of coronary artery-saphenous vein bypass.

The velocity distribution of a suspension of red blood cell ghosts in an idealized model of the coronary artery-saphenous vein bypass has been investigated with the aid of laser Doppler anemometry. Pulsatile flow simulated pressure variations in the ascending aorta and ghost cell velocities were determined by the Doppler shift of scattered laser light. Using four different model bypasses it was demonstrated that turbulent flow at the graft-coronary intersection can be delayed by decreasing the discontinuity in diameter between the bypass vein and coronary artery, and also by reducing the bypass vein and host coronary artery intersection angle.