A Comparison of Long-Term Outcomes in Patients Managed With Venovenous Extracorporeal Membrane Oxygenation in the First and Second Waves of the COVID-19 Pandemic in the United Kingdom.

OBJECTIVES: Early studies of venovenous extracorporeal membrane oxygenation (ECMO) in COVID-19 have revealed similar outcomes to historical cohorts. Changes in the disease and treatments have led to differences in the patients supported on venovenous ECMO in the first and second waves. We aimed to compare these two groups in both the acute and follow-up phase. DESIGN: Retrospective single-center cohort study comparing mortality at censoring date (November 30, 2021) and decannulation, patient characteristics, complications and lung function and quality of life (QOL-by European Quality of Life 5 Dimensions 3 Level Version) at first follow-up in patients supported on venovenous ECMO between wave 1 and wave 2 of the COVID-19 pandemic. SETTING: Critical care department of a severe acute respiratory failure service. PATIENTS: Patients supported on ECMO for COVID-19 between wave 1 (March 17, 2020, to August 31, 2020) and wave 2 (January 9, 2020, to May 25, 2021). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three patients were included in our analysis. Survival at censoring date (χ 2 , 6.35; p = 0.012) and decannulation (90.4% vs 70.0%; p < 0.001) was significantly lower in the second wave, while duration of ECMO run was longer (12.0 d [18.0-30.0 d] vs 29.5 d [15.5-58.3 d]; p = 0.005). Wave 2 patients had longer application of noninvasive ventilation (NIV) prior to ECMO and a higher frequency of barotrauma. Patient age and NIV use were independently associated with increased mortality (odds ratio 1.07 [1.01-1.14]; p = 0.025 and 3.37 [1.12-12.60]; p = 0.043, respectively). QOL and lung function apart from transfer coefficient of carbon monoxide corrected for hemoglobin was similar at follow-up across the waves. CONCLUSIONS: Most patients with COVID-19 supported on ECMO in both waves survived in the short and longer term. At follow-up patients had similar lung function and QOL across the two waves. This suggests that ECMO has an ongoing role in the management of a carefully selected group of patients with COVID-19.

Utility of echocardiographic right ventricular subcostal strain in critical care.

AIMS: Right ventricular (RV) strain is a known predictor of outcomes in various heart and lung pathologies but has been considered too technically challenging for routine use in critical care. We examined whether RV strain acquired from the subcostal view, frequently more accessible in the critically ill, is an alternative to conventionally derived RV strain in intensive care. METHODS AND RESULTS: RV strain data were acquired from apical and subcostal views on transthoracic echocardiography (TTE) in 94 patients (35% female), mean age 50.5 ± 15.2 years, venovenous extracorporeal membrane oxygenation (VVECMO) (44%). RV strain values from the apical (mean ± standard deviation; -20.4 ± 6.7) and subcostal views (-21.1 ± 7) were highly correlated (Pearson's r -0.89, P < 0.001). RV subcostal strain correlated moderately well with other echocardiography parameters including tricuspid annular plane systolic excursion (r -0.44, P < 0.001), RV systolic velocity (rho = -0.51, P < 0.001), fractional area change (r -0.66, P < 0.01), and RV outflow tract velocity time integral (r -0.49, P < 0.001). VVECMO was associated with higher RV subcostal strain (non-VVECMO -19.6 ± 6.7 vs. VVECMO -23.2 ± 7, P = 0.01) but not apical RV strain. On univariate analysis, RV subcostal strain was weakly associated with survival at 30 days (R2 = 0.04, P = 0.05, odds ratio =1.08) while apical RV was not (P = 0.16). CONCLUSION: RV subcostal deformation imaging is a reliable surrogate for conventionally derived strain in critical care and may in time prove to be a useful diagnostic marker in this cohort.

Six Month Mortality in Patients with COVID-19 and Non-COVID-19 Viral Pneumonitis Managed with Veno-Venous Extracorporeal Membrane Oxygenation.

A significant proportion of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) with high risk of death. The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) for COVID-19 on longer-term outcomes, unlike in other viral pneumonias, is unknown. In this study, we aimed to compare the 6 month mortality of patients receiving VV-ECMO support for COVID-19 with a historical viral ARDS cohort. Fifty-three consecutive patients with COVID-19 ARDS admitted for VV-ECMO to the Royal Brompton Hospital between March 17, 2020 and May 30, 2020 were identified. Mortality, patient characteristics, complications, and ECMO parameters were then compared to a historical cohort of patients with non-COVID-19 viral pneumonia. At 6 months survival was significantly higher in the COVID-19 than in the non-COVID-19 viral pneumonia cohort (84.9% vs. 66.0%, p = 0.040). Patients with COVID-19 had an increased Murray score (3.50 vs. 3.25, p = 0.005), a decreased burden of organ dysfunction (sequential organ failure score score [8.76 vs. 10.42, p = 0.004]), an increased incidence of pulmonary embolism (69.8% vs. 24.5%, p < 0.001) and in those who survived to decannulation longer ECMO runs (19 vs. 11 days, p = 0.001). Our results suggest that survival in patients supported with EMCO for COVID-19 are at least as good as those treated for non-COVID-19 viral ARDS.

Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology.Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia.Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography.Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29-79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6).Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.

Frequency of Thrombocytopenia and Heparin-Induced Thrombocytopenia in Patients Receiving Extracorporeal Membrane Oxygenation Compared With Cardiopulmonary Bypass and the Limited Sensitivity of Pretest Probability Score.

OBJECTIVES: To ascertain: 1) the frequency of thrombocytopenia and heparin-induced thrombocytopenia; 2) positive predictive value of the Pretest Probability Score in identifying heparin-induced thrombocytopenia; and 3) clinical outcome of heparin-induced thrombocytopenia in adult patients receiving venovenous- or venoarterial-extracorporeal membrane oxygenation, compared with cardiopulmonary bypass. DESIGN: A single-center, retrospective, observational cohort study from January 2016 to April 2018. SETTING: Tertiary referral center for cardiac and respiratory failure. PATIENTS: Patients who received extracorporeal membrane oxygenation for more than 48 hours or had cardiopulmonary bypass during specified period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data were collected retrospectively. Pretest Probability Score and heparin-induced thrombocytopenia testing results were collected prospectively. Mean age (± SD) of the extracorporeal membrane oxygenation and cardiopulmonary bypass cohorts was 45.4 (± 15.6) and 64.9 (± 13), respectively (p < 0.00001). Median duration of cardiopulmonary bypass was 4.6 hours (2-16.5 hr) compared with 170.4 hours (70-1,008 hr) on extracorporeal membrane oxygenation. Moderate and severe thrombocytopenia were more common in extracorporeal membrane oxygenation compared with cardiopulmonary bypass throughout (p < 0.0001). Thrombocytopenia increased in cardiopulmonary bypass patients on day 2 but was normal in 83% compared with 42.3% of extracorporeal membrane oxygenation patients at day 10. Patients on extracorporeal membrane oxygenation also followed a similar pattern of platelet recovery following cessation of extracorporeal membrane oxygenation. The frequency of heparin-induced thrombocytopenia in extracorporeal membrane oxygenation and cardiopulmonary bypass were 6.4% (19/298) and 0.6% (18/2,998), respectively (p < 0.0001). There was no difference in prevalence of heparin-induced thrombocytopenia in patients on venovenous-extracorporeal membrane oxygenation (8/156, 5.1%) versus venoarterial-extracorporeal membrane oxygenation (11/142, 7.7%) (p = 0.47). The positive predictive value of the Pretest Probability Score in identifying heparin-induced thrombocytopenia in patients post cardiopulmonary bypass and on extracorporeal membrane oxygenation was 56.25% (18/32) and 25% (15/60), respectively. Mortality was not different with (6/19, 31.6%) or without (89/279, 32.2%) heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation (p = 0.79). CONCLUSIONS: Thrombocytopenia is already common at extracorporeal membrane oxygenation initiation. Heparin-induced thrombocytopenia is more frequent in both venovenous- and venoarterial-extracorporeal membrane oxygenation compared with cardiopulmonary bypass. Positive predictive value of Pretest Probability Score in identifying heparin-induced thrombocytopenia was lower in extracorporeal membrane oxygenation patients. Heparin-induced thrombocytopenia had no effect on mortality.

Intracranial Hemorrhage and Early Mortality in Patients Receiving Extracorporeal Membrane Oxygenation for Severe Respiratory Failure.

Intracranial hemorrhage (ICH) is a serious complication in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) and is associated with high mortality. It is unknown whether ICH may be a consequence of the ECMO or of an underlying disease. The authors first aimed to assess the incidence of ICH at initiation and during the course of VV-ECMO and its associated mortality. The second aim was to identify clinical and laboratory measures that could predict the development of ICH in severe respiratory failure. Data were collected from a total number of 165 patients receiving VV-ECMO from January, 2012 to December, 2016 in a single tertiary center and treated according to a single protocol. Only patients who had a brain computed tomography within 24 hours of initiation of ECMO (n = 149) were included for analysis. The prevalence and incidence of ICH at initiation and during the course of VV-ECMO (at median 9 days) were 10.7% (16/149) and 5.2% (7/133), respectively. Thrombocytopenia and reduced creatinine clearance (CrCL) were independently associated with increased risk of ICH on admission; odds ratio (95% confidence interval): 22.6 (2.6-99.5), and 10.8 (5.6-16.2). Only 30-day (not 180-day) mortality was significantly higher in patients with ICH on admission versus those without (37.5% [6/16] vs 16.4% [22/133]; p = 0.03 and 43.7% [7/16] vs 26.3% [35/133]; p = 0.15, respectively). Reduced CrCL and thrombocytopenia were associated with ICH at initiation of VV-ECMO. The higher incidence of ICH at initiation suggests it is more closely related to the severity of the underlying lung injury than to the VV-ECMO itself. ICH at VV-ECMO initiation was associated with early mortality.

Hemodynamic coherence in sepsis.

Microvascular alterations are a hallmark of sepsis and play a crucial role in its pathophysiology. Such alterations are the result of overwhelming inflammation, which negatively affects all the components of the microcirculation. As the severity of microvascular alterations is associated with organ dysfunction and mortality, several strategies have been tested for improving microcirculation. Nevertheless, they are mainly based on the conventional manipulation of systemic hemodynamics to increase the total flow to the organs and tissues. Other therapeutic interventions are still being investigated. In this review, we discuss the pathophysiology of septic microcirculatory dysfunction and its implications for possible treatments.

Steal induction in preschool children: is melatonin as good as clonidine? A prospective, randomized study.

OBJECTIVES/AIMS: To investigate whether melatonin would be an alternative drug to clonidine for performance of steal induction. BACKGROUND: Distress during induction might have a negative impact on postoperative behavior. A steal induction is a technique for smooth anesthesia induction, and clonidine has been the primary agent for this purpose. There are conflicting results regarding the efficacy of melatonin for premedication, but its sleep inducing properties have been shown in children. METHODS: Pediatric patients ASA I and II were randomly assigned to receive either melatonin 0.3 mg·kg(-1) or clonidine 4 µg·kg(-1) orally. Primary outcome was the percentage of successful steal induction, while secondary outcomes were onset of sleep, overall quality of mask induction, and adverse events at emergence from anesthesia. RESULTS: A total of 87 patients were included for analysis with a median age of 33 months (range, 12-71) and median weight of 14 kg (range, 8-26). A successful steal induction was performed in 88.4% of group C and 75% of group M (P > 0.05). Onset of sleep in these patients occurred after a median time of 45 min (range 10-60) in group C and 35 min (range 15-60) in group M (P > 0.05). Children not falling asleep after melatonin received the premedication at a significantly earlier time point compared to those falling asleep (P = 0.001). CONCLUSIONS: Melatonin was effective for steal induction in 75% of children compared to 88% of children who had clonidine. Melatonin resulted less effective when administered early in the morning.

Intralesional steroid injection after endoscopic balloon dilation in pediatric Crohn's disease with stricture: a prospective, randomized, double-blind, controlled trial.

BACKGROUND: Endoscopic balloon dilation (EBD) is an attractive conservative therapy for Crohn's disease (CD) with stricture; however, its long-term efficacy has been questioned because many patients require more dilations or postdilation surgery. Most reports are retrospective, and no pediatric data are available. OBJECTIVE: To assess the effectiveness of corticosteroid intralesional injection after EBD in preventing stricture recurrence. DESIGN: Single-center prospective, randomized, double-blind, controlled trial. SETTING: Tertiary-referral university hospital. PATIENTS: Between November 2005 and January 2009, 29 pediatric patients with stricturing CD were enrolled. INTERVENTIONS: Enrolled patients were randomized to receive intrastricture injection of corticosteroid (CS) (n = 15) or placebo (n = 14) after EBD. Patients were followed clinically via small intestine contrast US and intestinal magnetic resonance imaging at 1, 3, 6, and 12 months; all underwent colonoscopy 12 months after dilation. MAIN OUTCOME MEASUREMENTS: Time free of repeat dilation and time free of surgery in the 2 groups. RESULTS: One of the 15 patients receiving CS required redilation, whereas the latter was needed in 5 of the 14 placebo patients; surgery was needed in 4 of the placebo patients, but in none of those receiving CS. The 2 groups statistically differed in the time free of redilation (P = .04) as well as for time free of surgery after EBD (P = .02), which were worse in the placebo group compared with the CS group. There were no significant differences in baseline demographics between the 2 groups. LIMITATIONS: Sample size, participation bias, and short-term follow-up. CONCLUSION: In pediatric CD with stricture, intralesional CS injection after EBD is an effective strategy for reducing the need both for redilation and surgery.

Low cervical skin crease approach for superior sternal cleft repair.

Superior sternal cleft repair aims to restore bony protection to mediastinal structures and to eliminate visible deformity. We describe a 4-day-old neonate with an isolated defect who successfully underwent primary repair using a low cervical skin crease incision. Such a novel approach combined optimal surgical exposure and excellent cosmesis.

Absorption pharmacokinetics of clonidine nasal drops in children.

BACKGROUND: The alpha2 agonist clonidine has become a popular drug for premedication in children. Effects and pharmacokinetics after oral, rectal, and intravenous administration are well known. The aim of this study was to investigate the absorption pharmacokinetics of clonidine nasal drops in children. METHODS: Thirteen ASA I pediatric patients received after induction of anesthesia 4 mcg x kg(-1) of clonidine by the nasal route. Blood samples were taken during a 12-h period and plasma levels of clonidine were analyzed by liquid chromatography-mass spectrometry. Data were calculated by a computer-aided curve-fitting program. RESULTS: Plasma pharmacokinetics following administration of clonidine nasal drops showed a considerable interindividual variability and absorption was delayed and limited. A total of 95% confidence intervals for maximum plasma concentration and time to achieve maximum plasma concentration were 0.4-0.6 ng x ml(-1) and 1.4-3.0 h, respectively. CONCLUSIONS: Clonidine nasal drops are erratically absorbed from the nasal mucosa and, thus, this mode of drug administration is not recommended for premedication purposes.

Premedication in children: a comparison of oral midazolam and oral clonidine.

BACKGROUND: Oral premedication is widely used in pediatric anesthesia to reduce preoperative anxiety and ensure smooth induction. Midazolam is currently the most commonly used premedicant, but good results have also been reported with clonidine. The aim of the present study was to compare clinical effects of oral midazolam and oral clonidine. METHODS: We performed a prospective open study in 64 children who were randomly assigned to receive either oral midazolam 0.5 mg.kg (-1) (group M) or oral clonidine 4 microg.kg (-1) (group C) prior to mask induction. Drug acceptance, preoperative sedation and anxiolysis, quality of mask acceptance, recovery profile and parental satisfaction were evaluated. RESULTS: The taste of oral clonidine was judged as significantly better; 14% of children rejected oral midazolam. Onset of sedation was significantly faster after premedication with midazolam (30+/-13.1 min) than with clonidine (38.5+/-14.6 min), but level of sedation was significantly better after premedication with clonidine. Quality of mask induction was equally successful in both groups. A steal-induction was performed in 66% of patients of group C, but none in group M. We observed a trend towards an increased incidence of emergence agitation after premedication with midazolam. Parental satisfaction was significantly higher in group C. CONCLUSIONS: In this study, premedication with oral clonidine appeared to be superior to oral midazolam. Quality of mask acceptance was comparable between groups, but oral clonidine was better accepted by the child, produced more effective preoperative sedation, showed a trend towards better recovery from anesthesia and had a higher degree of parental satisfaction.