Veno-arterial extracorporeal membrane oxygenation for circulatory failure in COVID-19 patients: insights from the ECMOSARS registry.

OBJECTIVES: The clinical profile and outcomes of patients with Coronavirus Disease 2019 (COVID-19) who require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or veno-arterial-venous extracorporeal membrane oxygenation (VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favourable and unfavourable outcomes. METHODS: ECMOSARS is a multicentre, prospective, nationwide French registry enrolling patients who require veno-venous extracorporeal membrane oxygenation (ECMO)/VA-ECMO in the context of COVID-19 infection (652 patients at 41 centres). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock. RESULTS: The median age was 49. Fourteen percent of patients had a prior diagnosis of heart failure. The most common aetiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%) and acute coronary syndrome (4%). Extracorporeal cardiopulmonary resuscitation (E-CPR) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day 1, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (P = 0.030 and P = 0.006). Other factors associated with death were greater age (P = 0.02), higher body mass index (P = 0.03), E-CPR (P = 0.001), non-myocarditis aetiology (P = 0.02), higher serum lactates (P = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (P = 0.003), haemorrhagic complications (P = 0.001), greater transfusion requirements (P = 0.001) and more severe Survival after Veno-Arterial ECMO (SAVE) and Sonographic Assessment of Intravascular Fluid Estimate (SAFE) scores (P = 0.01 and P = 0.03). CONCLUSIONS: We report the largest focused analysis of VA- and VAV-ECMO recipients in COVID-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population.

Impact of prolonged requirement for insulin on 90-day mortality in critically ill patients without previous diabetic treatments: a post hoc analysis of the CONTROLING randomized control trial.

BACKGROUND: Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments. METHODS: This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5. RESULTS: A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54-76) years. Median values for SAPS II and HbA1C were 50 (37.5-64) and 5.7 (5.4-6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality (IPTWHR = 1.22; CI 95% 0.84-1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 (IPTWHR = 3.34; CI 95% 1.26-8.83; p < 0.01). CONCLUSION: In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results.

Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study-a randomized clinical trial.

PURPOSE: Hyperglycaemia is an adaptive response to stress commonly observed in critical illness. Its management remains debated in the intensive care unit (ICU). Individualising hyperglycaemia management, by targeting the patient's pre-admission usual glycaemia, could improve outcome. METHODS: In a multicentre, randomized, double-blind, parallel-group study, critically-ill adults were considered for inclusion. Patients underwent until ICU discharge either individualised glucose control by targeting the pre-admission usual glycaemia using the glycated haemoglobin A1c level at ICU admission (IC group), or conventional glucose control by maintaining glycaemia below 180 mg/dL (CC group). A non-commercial web application of a dynamic sliding-scale insulin protocol gave to nurses all instructions for glucose control in both groups. The primary outcome was death within 90 days. RESULTS: Owing to a low likelihood of benefit and evidence of the possibility of harm related to hypoglycaemia, the study was stopped early. 2075 patients were randomized; 1917 received the intervention, 942 in the IC group and 975 in the CC group. Although both groups showed significant differences in terms of glycaemic control, survival probability at 90-day was not significantly different (IC group: 67.2%, 95% CI [64.2%; 70.3%]; CC group: 69.6%, 95% CI [66.7%; 72.5%]). Severe hypoglycaemia (below 40 mg/dL) occurred in 3.9% of patients in the IC group and in 2.5% of patients in the CC group (p = 0.09). A post hoc analysis showed for non-diabetic patients a higher risk of 90-day mortality in the IC group compared to the CC group (HR 1.3, 95% CI [1.05; 1.59], p = 0.018). CONCLUSION: Targeting an ICU patient's pre-admission usual glycaemia using a dynamic sliding-scale insulin protocol did not demonstrate a survival benefit compared to maintaining glycaemia below 180 mg/dL.

Septic shock complicated by disseminated herpes simplex virus-1 infection: a case report.

BACKGROUND: Herpes virus remains dormant in human cells and could reactivate under immunosuppressed conditions, such as prolonged critical illnesses. The phenomenon of viral replication during intensive care is well known, even in patients without a history of immunosuppression, but it usually does not have a clinical impact. Systemic reactivation leads to viral DNA in blood. It remains unclear whether this replication is a marker of morbimortality or a true pathogenic process. Therefore, it is unclear what medical treatment is most appropriate for simple replication. In organ damage suspected to be induced by herpes virus, there is no consensus on the most appropriate treatment duration. Here, we report a rarely described case of multiorgan failure implicating herpes simplex virus and discuss its treatment. CASE REPORT: A 53-year-old Caucasian immunosuppressed woman was admitted to the intensive care unit for septic shock. She presented pneumonia due to Klebsiella pneumoniae. Two weeks after admission, she showed multiorgan failure with acute respiratory distress syndrome and circulation failure. She had digestive and cutaneous lesions typical of herpes simplex virus 1. Blood and respiratory polymerase chain reaction was strongly herpes simplex virus-1 positive. No other bacteria, fungi, or viruses were found. The evolution was rapidly favorable after the initiation of antiviral treatment. Treatment was stopped after 3 weeks of well-conducted antiviral therapy. Curative-dose treatment was interrupted despite continuous strongly positive blood polymerase chain reaction results. In this context, prophylactic treatment was continued. CONCLUSION: We report an exceptional presentation of multiorgan failure in the intensive care unit due to herpes simplex virus-1. The diagnosis was made based on typical herpes simplex virus-1 visceral lesions and the absence of other responsible microorganisms. Intense viral replication is a key diagnostic element. There is no consensus regarding the most appropriate treatment duration, but such decisions should not be based on blood polymerase chain reaction.

Paradoxical Reaction to Hypnotics in Intensive Care Unit.

Background: Paradoxical reactions (PR) to benzodiazepines are well-known, but PR can also follow sedation by propofol, although this has been reported only in the context of operating room anesthesia. We report a rare case of paradoxical excitement induced by midazolam and propofol. Case presentation: A 78-year-old patient presented with multiorgan failure secondary to infectious pneumopathy. During intensive care unit (ICU) stay, he experienced 2 episodes of ventilator-acquired pneumonia and 1 of acute kidney failure requiring renal replacement therapy. Throughout the stay, he showed restlessness, uncontrollable muscle spasms and stiffness without any neurological focus. Paradoxical reaction to midazolam and to propofol was diagnosed; difficult withdrawal was followed by favorable progression. Conclusion: PR in the ICU context is exceptional. The present case is unique, with severe PR not only to midazolam but also to propofol. This etiology, with difficult withdrawal, should be considered after ruling out all classical etiologies for refractory agitation.

Assessing Renal Microvascular Reactivity by Laser Speckle-Contrast Imaging in Angiotensin-II-Treated Mice.

INTRODUCTION: The kidney is one of the main organs affected by microvascular damage wrought by hypertension. We developed an approach to investigate renal microcirculatory disturbance in live mice by measuring post-occlusive reactive hyperemia (PORH), a reactivity test exploring endothelial and neuro-microvascular functioning. Laser speckle-contrast analysis (LASCA) assesses microvascular blood flow; it provides real-time images of spatial and temporal blood flow dynamics. We compared basal blood flow and PORH test between control and angiotensin-II-treated mice (Ang-II) to validate the model. OBJECTIVE: The study objective was to develop an approach to investigate renal microcirculation, and then to compare microvascular reactivity assessed on LASCA in control versus Ang-II mice. METHODS: Thirty 7-week-old wild-type C57BL/6J mice were allocated into two groups. One received angiotensin-II via osmotic minipumps (Ang-II; n=15); the other served as control (n=15). Basal blood flow was measured on LASCA. The PORH test was then performed in the two groups. RESULTS: Control mice had significantly lower basal renal microcirculatory flow, expressed in perfusion units (PU), than Ang-II-treated mice (1448 ± 96 vs 1703 ± 185 PU, respectively; P < 0.05). Peak flow was lower in controls than in Ang-II mice (1617±104 vs.1724 ± 205 PU, respectively; P=0.21). Control mice had significantly higher kidney PORH than Ang-II mice (8±3 vs 1±4%, respectively; P < 0.05). CONCLUSION: We developed an innovative technique to study renal microcirculation in mice. Ang-II-treated mice showed significantly higher basal blood flow than controls, while PORH was significantly higher in controls than in Ang-II mice.

Mottling score and skin temperature in septic shock: Relation and impact on prognosis in ICU.

INTRODUCTION: Mottling score, defined by 5 areas over the knee is developed to evaluate tissue perfusion at bedside. Because of the subjective aspect of the score, we aimed to compare mottling score and skin temperature in septic shock with infrared thermography in ICU and the correlation to survival. METHODS: We conducted a prospective and observational study in a teaching hospital in France during 8 months in ICU. All patients with sepsis requiring vasoactive drugs were included. We recorded epidemiologic data, hemodynamic parameters, mottling score and skin temperature with a thermic camera of the 5 mottling areas around the knee (temperatures recorded with FLIR™ software) at bedside. Measures were performed at ICU admission (H0) and six hours after initial resuscitation (H6). RESULTS: 46 patients were included. Median age was 69 (60-78), SOFA score 11 (8-12) mean SAPS II was 57±20 and 28-day mortality rate was 30%. Patients with mottling (score≥1), had a skin temperature of the knee significantly lower (30.7 vs 33,2°C p = 0.01 at H6) than patients without mottling (score = 0). Skin temperatures of the knee in mottling groups 1 to 5 were similar at H0 and H6. Neither mottling score nor skin temperature of the knee were associated with prognostic regarding day-28 mortality. CONCLUSIONS: Skin temperature measured with infrared thermography technology around the knee is lower when mottling sign is present and sign microcirculation alterations. This method, compared to standard mottling score is objective and allows data collections. However, this method failed to predict mortality in ICU patients.

A new site for venous access: superficial veins of portal collateral circulation.

In case of failure of peripheral vascular access, classical alternatives are central venous or intraosseous access. We report a new site of vascular access necessitating no specific material. A 53-year-old patient with cirrhosis-induced coagulopathy, portal hypertension, and collateral abdominal portosystemic circulation required parenteral antibiotherapy. After failure of peripheral vein catheterization, he was addressed to our resuscitation room for central venous access. To avoid the risks associated with this invasive procedure, we chose an alternative approach. After skin preparation, a 20-gauge peripheral venous catheter was inserted in a dilated subcutaneous vein of abdominal wall. To our knowledge, it is the first human report of insertion of a catheter in a superficial vein of abdominal wall. It could be an alternative approach for vascular access after failure of peripheral venipuncture in patients with portal hypertension.