Outcomes of Extracorporeal Membrane Oxygenation (ECMO) for COVID-19 Patients: A Multi-Institutional Analysis.

BACKGROUND: In March 2020, COVID-19 was announced as a global pandemic. The first COVID-19 patient was connected to an ECMO device in Israel during that time. Since then, over 200 patients have required ECMO support due to COVID-19 infection. The present study is a multi-institutional analysis of all COVID-19 patients requiring veno-venous (VV) ECMO in Israel. The aim was to characterize and compare the survivors and deceased patients as well as establish risk factors for mortality. METHODS: This retrospective multi-institutional study was conducted from March 2020 to March 2021 in eleven of twelve ECMO centers operating in Israel. All COVID-19 patients on VV ECMO support were included in the cohort. The patients were analyzed based on their comorbidities, procedural data, adverse event on ECMO, and outcomes. Univariate and multivariate analyses were used to compare the deceased and the surviving patients. RESULTS: The study included 197 patients, of which 150 (76%) were males, and the mean age was 50.7 ± 12 years. Overall mortality was 106 (54%). Compared with the deceased subjects, survivors were significantly younger (48 ± 11 vs. 53 ± 12 years), suffered less from ischemic heart disease (IHD) (3% vs. 12%), and were ventilated for a significantly shorter period (≤4 days) prior to cannulation (77% vs. 63%). Patients in the deceased group experienced more kidney failure and sepsis. Rates of other complications were comparable between groups. CONCLUSIONS: Based on this study, we conclude that early cannulation (≤4 days) of younger patients (≤55 years) may improve overall survival and that a history of IHD might indicate a reduced prognosis.

Parasympathetic Versus Sympathetic Changes in Heart Rate Variability After a Multimodal Integrative Medicine Intervention for Frontline COVID-19 Personnel.

OBJECTIVE: Frontline healthcare providers (HCPs) working in COVID-19 hospital departments need to deal with considerable physical and emotional stress on a daily basis. We conducted a pilot study to examine changes in heart rate variability (HRV) in frontline COVID-19 personnel after an integrative medicine (IM) intervention. METHODS: HCPs working in isolated COVID-19 inpatient departments underwent a single 30-minute individually tailored IM sessions combining various IM modalities (acupuncture, mind-body, and/or manual-movement modalities, including anthroposophic medicine). HRV parameters were compared during the first IM session at 3-minute intervals, at the beginning of treatments, and after 20 minutes. Root mean square of successive RR interval differences (RMSSD) was measured, as were domains of time (standard deviation of NN intervals, percentage of successive RR intervals that differ by more than 50 milliseconds) and frequency (low frequency/high frequency [LF/HF] ratio). Preintervention and postintervention concerns were assessed using the Measure Yourself Concerns and Well-being questionnaire, with posttreatment free-text narratives analyzed for clusters of emotional- and spiritual-related keywords (ESKs). RESULTS: A total of 114 HCPs underwent an IM treatment session, and their HRV values were measured, of which 75 (65.8%) expressed ESKs. The RMSSD increased only in the ESK-expressing group ( p < .001). LF/HF ratios decreased in both groups, with HF power increasing in the ESK-expressing ( p = .043) and LF power decreasing in the non-ESK-expressing groups ( p = .004). CONCLUSIONS: Increased parasympathetic activity was observed in all HCPs after the IM intervention, particularly among those expressing ESKs. LF/HF parameters suggest different relaxation-associated mechanisms, with increased HF (regulated predominantly by parasympathetic tone) in the ESK-expressing and decreased LF (regulated partially by sympathetic tone) in the nonexpressing group. Additional research needs to explore the relationship between subjective effects of the IM intervention and physiological mechanisms of relaxation in HCPs working in stressful environments. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05104827.

Complementary and integrative medicine intervention in front-line COVID-19 clinicians.

OBJECTIVE: To assess the impact of a multidisciplinary complementary and integrative medicine (CIM) intervention on physical and emotional concerns among front-line COVID-19 healthcare providers (HCPs). METHODS: A multimodality CIM treatment intervention was provided by integrative practitioners to HCPs in three isolated COVID-19 departments. HCPs' two main concerns were scored (from 0 to 6) before and following the CIM intervention using the Measure Yourself Concerns and Wellbeing questionnaire. Postintervention narratives identified reflective narratives specifying emotional and/or spiritual keywords. RESULTS: Of 181 HCPs undergoing at least one CIM treatment, 119 (65.7%) completed post-treatment questionnaires. While HCPs listing baseline emotional-related concerns benefited from the CIM intervention, those who did not express emotional or spiritual concerns improved even more significantly following the first session, for both leading concerns (p=0.038) and emotional-related concerns (p=0.023). Nevertheless, it was shown that following subsequent treatments HCPs who expressed emotional and spiritual concerns improved more significantly than those who did not for emotional-related concerns (p=0.017). CONCLUSIONS: A CIM intervention for front-line HCPs working in isolated COVID-19 departments can significantly impact emotional-related concerns, more so after the first treatment and among HCPs not using emotional-spiritual keywords in post-treatment narratives. Referral of HCPs to CIM programmes for improved well-being should avoid referral bias to those not expressing emotional/spiritual concerns.

Sensing the lightness: a narrative analysis of an integrative medicine program for healthcare providers in the COVID-19 department.

OBJECTIVES: The research addressing physical and emotional exhaustion among healthcare providers (HCPs) in COVID-19 departments is limited. We examined the impact of integrative medicine (IM) intervention for HCPs working in isolated COVID-19 in-patient departments, addressing concerns and well-being. METHODS: HCPs working in 3 isolated COVID-19 in-patient departments underwent 40-min IM treatment sessions (including acupuncture, manual movement, and/or mind-body modalities) provided by integrative oncology practitioners. The MYCAW (Measure Yourself Concerns and Well-being) questionnaire examined HCP concerns and free-text narratives following IM treatments. Data were qualitatively analyzed using ATLAS.Ti software for systematic coding. RESULTS: A total of 181 HCPs underwent 305 IM treatments. Narrative themes focused on physical symptoms (primarily pain and fatigue) and emotional concerns, including perceived communication barriers with patients, and reflections on well-being and insights following IM treatments. HCPs reported feeling a sense of "relief" which was likely related to the 3 main effects of the IM intervention: a sense of "being cared for" and treated; experiencing emotional, sometimes spiritual effects of the treatment; and the feeling of relaxation, combined with the relief of pain. Qualitative analysis identified clusters of emotional and spiritual-related keywords such as "calming," "release," "relaxation," and "disengagement" following the first IM session (119 of 181 narratives, 65.7%). CONCLUSIONS: HCPs working in isolated COVID-19 departments reported improved well-being and the addressing of their concerns following IM treatment sessions provided during their work shift. Further research is needed to explore the impact of IM on HCP burnout and resilience in palliative care settings.

Empty SV40 capsids increase survival of septic rats by eliciting numerous host signaling networks that participate in a number of systemic functions.

Sepsis is an excessive, dysregulated immune response to infection that activates inflammatory and coagulation cascades, which may lead to tissue injury, multiple organ dysfunction syndrome and death. Millions of individuals die annually of sepsis. To date, the only treatment available is antibiotics, drainage of the infection source when possible, and organ support in intensive care units. Numerous previous attempts to develop therapeutic treatments, directed at discreet targets of the sepsis cascade, could not cope with the complex pathophysiology of sepsis and failed. Here we describe a novel treatment, based on empty capsids of SV40 (nanocapsids - NCs). Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%. Transcript analyses (RNAseq) demonstrated that the NC treatment is a paradigm shift. The NCs affect multiple facets of biological functions. The affected genes are modified with time, adjusting to the recovery processes. The NCs effect on normal control rats was negligible. The study shows that the NCs are capable of coping with diseases with intricate pathophysiology. Further studies are needed to determine whether when applied after sepsis onset, the NCs still improve outcome.

WHO Needs High FIO2?

World Health Organization and the United States Center for Disease Control have recently recommended the use of 0.8 FIO2 in all adult surgical patients undergoing general anaesthesia, to prevent surgical site infections. This recommendation has arisen several discussions: As a matter of fact, there are numerous studies with different results about the effect of FIO2 on surgical site infection. Moreover, the clinical effects of FIO2 are not limited to infection control. We asked some prominent authors about their comments regarding the recent recommendations.

Multicentre validation of manufacturers' weight-based recommendations for laryngeal mask airway size choice in anaesthetic practice: A retrospective analysis of 20,893 cases.

BACKGROUND: Manufacturers' weight-based recommendations for laryngeal mask airway (LMA) sizes are not scientifically founded and have never been validated clinically. OBJECTIVE: The validation of manufacturers' weight-based recommendations in clinical practice and whether other patient variables such as sex and age may influence LMA size choice. DESIGN: A retrospective study. SETTING: Four Israeli hospitals (two tertiary and two secondary hospitals). METHODS: Data on LMA use were retrieved from the Anaesthesia Information Management System (AIMS). Multinomial logistic regression analysis including weight, sex and age amongst adults, adolescents and children was used to identify predictors of LMA size used (development data set). Concordance between the size of LMA used and that predicted according to the model and the manufacturers' recommendations was assessed (validation data set). RESULTS: LMA insertions were analysed in 13,743 (65.8%) adults, 1807 (8.6%) adolescents and 5343 (25.6%) children. Suitability of manufacturers' recommendations was higher in children [4075/5343 (76.3%)] than adults [5200/13743 (37.8%)] or adolescents [885/1807 (49.0%); P < 0.001 for children vs. adults or adolescents]. Sex influenced LMA size in adults and adolescents, but not in children. Age had no influence. Amongst adults and adolescents, LMA size was better predicted by the regression model than by manufacturers' recommendations [adults: anaesthetists/model 61.7%, 95% confidence interval (95% CI) 60.1 to 63.2, anaesthetists/manufacturer 38.4%, 95% CI 36.0 to 39.0, P < 0.001; adolescents: anaesthetists/model 68.1%, 95% CI 64.1 to 72.0, anaesthetists/manufacturer 46.9%, 95% CI 42.7 to 51.1, P < 0.001]. In children, the regression model and manufacturers' weight-based recommendations performed equally (anaesthetists/model 78.0%, 95% CI 75.9 to 80.0, anaesthetists/manufacturer 75.7%, 95% CI 73.6 to 7.8, P = 0.126). CONCLUSION: Manufacturers' weight-based recommendations for LMA size reflect clinical practice in children, but not in adults and adolescents. In these age groups, choice of LMA size is influenced by sex and weight, although with wider ranges than those recommended by manufacturers.

Perioperative goal-directed hemodynamic optimization using noninvasive cardiac output monitoring in major abdominal surgery: a prospective, randomized, multicenter, pragmatic trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery).

BACKGROUND: In this study, our objective was to determine whether a perioperative hemodynamic protocol based on noninvasive cardiac output monitoring decreases the incidence of postoperative complications and hospital length of stay in major abdominal surgery patients requiring intensive care unit admission. Secondary objectives were the time to peristalsis recovery and the incidence of wound infection, anastomotic leaks, and mortality. METHODS: A randomized clinical trial was conducted in 6 tertiary hospitals. One hundred forty-two adult patients scheduled for open colorectal surgery, gastrectomy, or small bowel resection were enrolled. A hemodynamic protocol including fluid administration and vasoactive drugs based on arterial blood pressure, cardiac index, and stroke volume response was compared with standard practice. Patients were followed until hospital discharge (determined by a surgeon blinded to the study) or death. In contrast to previous studies, we designed a pragmatic trial (as opposed to explanatory trials) to mimic real practice and obtain maximal external validity for the study. RESULTS: Fluid administration was similar except for the number of colloid boluses (2.4 ± 1.8 [treated] vs 1.3 ± 1.4 [control]; P < 0.001) and packed red blood cell units (0.6 ± 1.3 [treated] vs 0.2 ± 0.6 [control]; P = 0.019). Dobutamine was used in 25% (intraoperatively) and 19.4% (postoperatively) of the treated patients versus 1.4% and 0% in the control group (P < 0.001). We have observed a reduction in reoperations in the treated group (5.6% vs 15.7%; P = 0.049). However, no significant differences were observed in overall complications (40% vs 41%; relative risk 0.99 [0.67-1.44]; P = 0.397), length of stay (11.5 [8-15] vs 10.5 [8-16]; P = 0.874), time to first flatus (62 hours [40-76] vs 72 hours [48-96]; P = 0.180), wound infection (7 vs 14; P = 0.085), anastomotic leaks (2 vs 5; P = 0.23), or mortality (4.2% vs 5.7%; P = 0.67). CONCLUSIONS: The results of our pragmatic study indicate that a perioperative hemodynamic protocol guided by a noninvasive cardiac output monitor was not associated with a decrease in the incidence of overall complications or length of stay in major abdominal surgery.

Hand-assisted laparoscopic surgery for liver tumors.

BACKGROUND: The surgical treatment for liver tumors, whether metastatic or hepatic in origin, traditionally used the open approach through large incisions. In recent years the laparoscopic approach became popular but few centers use this method routinely. OBJECTIVES: To assess the results of our initial experience with liver resection using the laparoscopic approach, in terms of patient safety and oncologic surgical outcome. METHODS: Between August 2007 and April 2008 we performed 10 liver resections in 9 patients using the hand-assisted laparoscopic surgery technique. RESULTS: The main indication for surgery was metastatic colorectal carcinoma in seven patients and hepatocellular carcinoma in two. The mean age was 67 +/- 11 years. The tumor was solitary in seven patients. Five patients had neoadjuvant chemotherapy. Altogether, 12 lesions with an average size of 17 +/- 9 mm were resected. The mean operative time was 180 +/- 52 minutes. Average postoperative stay was 6.5 +/- 3.5 days. There was no perioperative mortality. There was one conversion to open surgery due to bleeding from the left hepatic vein. No major perioperative complications were encountered. All resected margins were free of malignancy. CONCLUSIONS: Liver resection using HALS is safe and feasible and should be considered in selected patients.

Arterial and plethysmographic waveform analysis in anesthetized patients with hypovolemia.

BACKGROUND: Respiratory-induced arterial and plethysmographic (pulse oximetry) waveform changes were shown to be good predictors of cardiac output response to increased preload. The aim of this study was to evaluate the reliability of arterial and plethysmographic waveform variables in patients with mild hypovolemia. METHODS: Patients undergoing autologous hemodilution were studied. After anesthesia induction, hemodilution was performed by withdrawing blood in steps of 2% of estimated circulating blood volume (ECBV), up to 20%. The patients who did not develop hypotension (systolic blood pressure < 80 mmHg) were studied. Arterial and plethysmographic waveforms were recorded and analyzed off-line at baseline and after each withdrawal of blood. Variations in arterial systolic and pulse pressure were analyzed using standard methods. Plethysmographic waveform variation and delta pulse oximetry plethysmography were determined by using pulse oximetry recordings. RESULTS: There were 33 study participants. Systolic blood pressure decreased by 11%, and heart rate increased from 73 to 76 beats/min after a 20% reduction of ECBV. Systolic pressure and pulse pressure variations increased (P < 0.005) after a 4% reduction of ECBV. The values of arterial pressure and pulse oximetry waveform variables almost doubled in value after a 20% reduction of ECBV. Systolic pressure variation was the most reliable variable during hypovolemia. Plethysmographic waveform variation increased significantly after a 6% reduction of ECBV and delta pulse oximetry plethysmography after an 8% reduction of ECBV. CONCLUSIONS: Arterial and pulse oximetry respiratory-induced changes in waveform variables are reliable indicators of mild hypovolemia in anesthetized patients. The pulse oximetry plethysmographic waveforms accurately reflect arterial waveforms during more progressive hypovolemia.

The effect of acute autologous blood transfusion on coagulation dysfunction after cardiopulmonary bypass.

OBJECTIVE: To evaluate the influence of acute autologous blood transfusion on postcardiopulmonary bypass coagulation disturbances evaluated by thromboelastography (TEG) as a point-of-care test. METHODS: This prospective randomized controlled study included consecutive patients who underwent elective cardiac surgery with cardiopulmonary bypass. The patients in group A underwent acute autologous blood transfusion with acute normovolemic haemodilution and those in group H received homologous blood, if needed, and served as controls. RESULTS: A total of 62 patients, from 68 enrolled, completed the study: 27 in group A and 35 in group H. Both groups had similar prolongation of prothrombin time and partial thromboplastin time, decreased platelets count and changes in postoperative thromboelastographic variables. There were no differences between them for postoperative bleeding, blood transfusions or haemoglobin values. There was significant prolongation of the R value of TEG (without heparinase) in both groups at 4 h after surgery compared with the immediate postoperative values: from 11.3 +/- 4.2 to 12.3 +/- 5.5 mm, P < 0.05 for group A and from 9.9 +/- 3.7 to 12.5 +/- 5.4 mm, P < 0.01 for group H. The R values of TEG with and without heparinase differed significantly (P < 0.05) at 4 h postoperatively. CONCLUSION: Autologous blood transfusion of 15% estimated blood volume did not affect postcardiopulmonary bypass coagulopathy, nor did it decrease blood loss or homologous blood and its products transfusion in the early postoperative period. TEG is a valuable measure for detecting coagulation dysfunction with a potential role in the postoperative management of cardiac patients.

The impact of an electronic reminder on the use of alarms after separation from cardiopulmonary bypass.

INTRODUCTION: During cardiopulmonary bypass (CPB) monitor alarms are routinely disabled. Failure to reactivate these alarms after CPB may jeopardize patient safety. We have produced an electronic reminder that automatically alerts clinicians to reactivate alarms after CPB and have evaluated the alarm reactivation rate after its implementation. METHODS: We developed and implemented an algorithm that identifies separation from CPB by the return of pulsatile flow and of mechanical ventilation, and checks alarm status (activated, disabled or silenced). If alarms have not been reactivated after separation from CPB, an electronic reminder appears. Data were collected during three time periods: Stage I (304 patients)--baseline period before implementation of the electronic reminder; Stage II (256 patients)--after implementation; Stage III-(435 patients) after a single educational departmental meeting, at the end of Stage II. Incidence of proper alarm reactivation and the number of electronic reminders per patient were compared among stages. RESULTS: The rate of alarm reactivation at baseline (Stage I) was 22%, increased to 63% (Stage II), and again to 83% during Stage III (P < 0.001). The spontaneous alarm reactivation rate before the appearance of the electronic reminder on the anesthesia information management system screen increased from 19% at Stage II to 42% at stage III (P < 0.001). CONCLUSION: Introducing an automatic electronic reminder significantly increased the rate of alarm reactivation after separation from CPB. Real-time computerized decision-support tools can be developed within anesthesia information management system and may be useful for improving safety during anesthesia.

DNA-free recombinant SV40 capsids protect mice from acute renal failure by inducing stress response, survival pathway and apoptotic arrest.

Viruses induce signaling and host defense during infection. Employing these natural trigger mechanisms to combat organ or tissue failure is hampered by harmful effects of most viruses. Here we demonstrate that SV40 empty capsids (Virus Like Particles-VLPs), with no DNA, induce host Hsp/c70 and Akt-1 survival pathways, key players in cellular survival mechanisms. We postulated that this signaling might protect against organ damage in vivo. Acute kidney injury (AKI) was chosen as target. AKI is critical, prevalent disorder in humans, caused by nephrotoxic agents, sepsis or ischemia, via apoptosis/necrosis of renal tubular cells, with high morbidity and mortality. Systemic administration of VLPs activated Akt-1 and upregulated Hsp/c70 in vivo. Experiments in mercury-induced AKI mouse model demonstrated that apoptosis, oxidative stress and toxic renal failure were significantly attenuated by pretreatment with capsids prior to the mercury insult. Survival rate increased from 12% to >60%, with wide dose response. This study demonstrates that SV40 VLPs, devoid of DNA, may potentially be used as prophylactic agent for AKI. We anticipate that these finding may be projected to a wide range of organ failure, using empty capsids of SV40 as well as other viruses.