Venovenous extracorporeal membrane oxygenation for COVID-19 associated severe respiratory failure: Case series from a Hungarian tertiary centre.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (V-V ECMO) is recommended for the support of patients with severe COVID-19 associated severe respiratory failure (SRF). We report the characteristics and outcome of COVID-19 patients supported with V-V ECMO in a Hungarian centre. METHODS: We retrospectively collected data on all patients admitted with proven SARS CoV-2 infection who received V-V ECMO support between March 2021 and May 2022. RESULTS: Eighteen patients were placed on ECMO during this period, (5 women, age (mean ± SD) 44 ± 10 years, APACHE II score (median (interquartile range)) 12 (10-14.5)). Before ECMO support, they had been hospitalised for 6 (4-11) days. Fifteen patients received noninvasive ventilation for 4 (2-8) days, two patients had high flow nasal oxygen therapy, for one day each. They had already been intubated for 2.5 (1-6) days. Prone position was applied in 15 cases. On the day before ECMO initiation the Lung Injury Score was 3.25 (3-3.26), the PaO2/FiO2 ratio was 71 ± 19 mmHg. The duration of V-V ECMO support was 26 ± 20 days, and the longest run lasted 70 days. Patients were mechanically ventilated for 34 ± 23 days. The intensive care unit (ICU) and the hospital length of stay were 40 ± 28 days and 45 ± 31 days, respectively. Eleven patients were successfully weaned from ECMO. The ICU survival rate was 56%, the in-hospital survival was 50%. All patients who were discharged from hospital reported a good health-related quality of life Rankin score (0-2) at the 5-16 months follow-up. CONCLUSIONS: During the last three waves of the COVID-19 pandemic, we achieved a 56% ICU and a 50% hospital survival rate at our low volume centre.

Respiratory consequences of obesity and diabetes / Az elhízás és a cukorbetegség légzorendszeri következményei

Összefoglaló. Bevezetés: A cukorbetegségben no a simaizmok tónusa, és megváltozik az elasztin és a kollagén szerkezete. Mivel a tüdoszövetben ezek a strukturális elemek meghatározóak, a cukorbetegség várhatóan módosítja a légutak és a tüdoszövet mechanikai és funkcionális viselkedését. Célkituzés: Vizsgálatunk során diabetesben szenvedo, elhízott és nem elhízott betegeink körében tanulmányoztuk a légzésmechanikai elváltozásokat és a gázcserefunkciót. Módszer: Elektív szívsebészeti beavatkozásra kerülo, normál testalkatú betegeket diabetesben nem szenvedo (n = 80), illetve cukorbeteg (n = 35) csoportokra osztottuk. További két betegcsoportba elhízott és nem cukorbeteg (n = 47), valamint elhízott és diabetesben szenvedo (n = 33) betegek kerültek. A légzorendszer mechanikai tulajdonságait kényszerített oszcillációs technikával határoztuk meg, mellyel a légúti ellenállás (Raw), valamint a szöveti csillapítás (G) és rugalmasság (H) tényezoi jellemezhetok. Volumetriás kapnográfia segítségével a kapnogram 3. fázisának meredekségét és a légzési térfogat különbözo ventilációs/perfúziós illeszkedési zavaraiból adódó holttérfrakciókat határoztuk meg. Az intrapulmonalis shuntfrakciót és az oxigenizációs indexet (PaO2/FiO2) artériás és centrális vénás vérgázmintákból határoztuk meg. Eredmények: A megfelelo kontrollcsoportokhoz hasonlítva a cukorbetegség önmagában is növelte az Raw (7,4 ± 5 vs. 3,0 ± 1,7 H2Ocm.s/l), a G (11,3 ± 4,9 vs. 6,2 ± 2,4 H2Ocm/l) és a H (32,3 ± 12,0 vs. 25,1± 6,9 H2Ocm/l) értékét (p<0,001 mindegyik betegcsoportnál), de ez nem járt együtt a gázcserefunckció romlásával. Hasonló patológiás elváltozásokat észleltünk elhízás során a légzésmechanikában és az alveolaris heterogenitásban, amelyek azonban a gázcsere hatékonyságát is rontották. Következtetés: Cukorbetegségben a légzésmechanika romlását a fokozott hypoxiás pulmonalis vasoconstrictio ellensúlyozni képes, ezzel kivédve az intrapulmonalis shunt növekedését és az oxigenizációs képesség romlását. Orv Hetil. 2022; 163(2): 63-73. INTRODUCTION: While sustained hyperglicemia affects the smooth muscle tone and the elastin-collagen network, the effect of diabetes mellitus on the function and structure of the airways and the lung parenchyma has not been characterized, and the confounding influence of obesity has not been elucidated. OBJECTIVE: To reveal the separate and additive roles of diabetes mellitus and obesity on the respiratory function. METHOD: Non-obese mechanically ventilated patients were categorized as control non-diabetic (n = 80) and diabetic (n = 35) groups. Obese patients with (n = 33) or without (n = 47) associated diabetes were also enrolled. Forced oscillation technique was applied to measure airway resistance (Raw), tissue damping (G), and tissue elastance (H). Capnography was utilized to determine phase 3 slopes and ventilation dead space parameters. Arterial and central venous blood samples were analyzed to assess intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FiO2). RESULTS: Diabetes without obesity increased the Raw (7.4 ± 5 cmH2O.s/l vs. 3.0 ± 1.7 cmH2O.s/l), G (11.3 ± 4.9 cmH2O/l vs. 6.2 ± 2.4 cmH2O/l), and H (32.3 ± 12.0 cmH2O/l vs. 25.1 ± 6.9 cmH2O/l, (p<0.001 for all), compared with the corresponding control groups. Capnographic phase 3 slope was increased in diabetes without significant changes in PaO2/FiO2 or Qs/Qt. While similar detrimental changes in respiratory mechanics and alveolar heterogeneity were observed in obese patients without diabetes, these alterations also compromised gas exchange. CONCLUSION: The intrinsic mechanical abnormalities in the airways and lung tissue induced by diabetes are counterbalanced by hypoxic pulmonary vasoconstriction, thereby maintaining intrapulmonary shunt fraction and oxygenation ability of the lungs. Orv Hetil. 2022; 163(2): 63-73.

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Extracorporeal membrane oxygenation in intensive care unit / Extracorporalis membránoxigenizáció intenzív osztályon.

Összefoglaló. Az extracorporalis membránoxigenizációt egyre gyakrabban alkalmazzák világszerte refrakter légzési és/vagy keringési elégtelenség kezelésében. Intézetünkben 2015-ben kezdtük meg a program elokészítését és felépítését. Célunk az extracorporalis membránoxigenizációs kezelés élettani alapjainak rövid ismertetése, különös tekintettel a venovenosus konfigurációra, és az eddig kezelt eseteink eredményeinek összefoglalása. Az irodalom szisztematikus áttekintése és a kezelt esetek adatainak retrospektív értékelése voltak a módszereink. 2016 óta összesen 14 beteg esetében használtunk extracorporalis membránoxigenizációt (8 férfi, 6 no, életkor 51 ± 15 év, APACHE II. score 24 ± 7). Az indikáció 9 esetben súlyos refrakter hypoxaemiás légzési elégtelenség, 1 esetben tracheooesophagealis fistula és légzési elégtelenség, 1 esetben mutét alatti támogatás tervezett trachearekonstrukció során és 3 beteg esetében refrakter cardiogen shock volt. Az extracorporalis membránoxigenizáció 11 betegben a légzés, 3 betegben a keringés támogatását szolgálta, 13 venovenosus, 1 venoarteriosus konfigurációban. Az extracorporalis támogatás ideje légzéstámogatás esetében 14 ± 6 nap, a cardialis támogatások esetében 5 ± 4 nap volt. Az intenzív osztályos ápolási ido 27 ± 13, illetve 21 ± 17 nap volt a két betegcsoportban. 9 beteget jó funkcionális állapotban bocsátottunk el, 5 beteg halt meg osztályunkon, további 3 késobb a kórházi bennfekvés során. Az extracorporalis membránoxigenizációs program regionális centrumokban Magyarországon is megvalósítható. A nemzetközi ajánlások, oktatási módszerek alkalmazásával a nemzetközi irodalomban közölt túlélési eredményekhez hasonló eredmények érhetok el hazánkban is. Orv Hetil. 2021; 162(11): 425-431. Summary. Extracorporeal membrane oxygenisation is commonly used worldwide for refractory respiratory and circulatory failure. We started to organise the introduction of this therapeutic modality in 2015. Our aim is to give a short review about extracorporeal life support, especially veno-venous extracorporeal membrane oxygenation, and to present our first results. We provide a systematic review of the currently available literature and a summary of our first treatments. As of 2016, we supported 14 patients with extracorporeal membrane oxygenisation (8 men, age 51 ± 15 years, APACHE II score 24 ± 7). The indications were refractory hypoxaemic respiratory failure in 9, tracheo-oesophageal fistula and respiratory failure in 1, support during surgery for planned tracheal reconstruction in 1, and refractory cardiogenic shock in 3 patients. We provided respiratory support in 11, circulatory support in 3 cases, with 13 veno-venous and 1 veno-arterial configuration. The support lasted for 14 ± 6 days in respiratory, and for 5 ± 4 days in cardiac cases. Intensive care length of stay was 27 ± 13 and 21 ± 17 days in the two patient groups. We discharged 9 patients in good functional state, 5 patients died during intensive care and further 3 later, during the hospital stay. Our results show that the implementation of an extracoporeal membrane oxygenation program is feasible in Hungarian tertiary centers. In line with international recommendations and adapting international training courses, the survival is very similar to that reported in the literature. Orv Hetil. 2021; 162(11): 425-431.

Use of capnography to verify emergency ventilator sharing in the COVID-19 era.

Exacerbation of COVID-19 pandemic may lead to acute shortage of ventilators, which may require shared use of ventilator as a lifesaving concept. Two model lungs were ventilated with one ventilator to i) test the adequacy of individual tidal volumes via capnography, ii) assess cross-breathing between lungs, and iii) offer a simulation-based algorithm for ensuring equal tidal volumes. Ventilation asymmetry was induced by placing rubber band around one model lung, and the uneven distribution of tidal volumes (VT) was counterbalanced by elevating airflow resistance (HR) contralaterally. VT, end-tidal CO2 concentration (ETCO2), and peak inspiratory pressure (Ppi) were measured. Unilateral LC reduced VT and elevated ETCO2 on the affected side. Under HR, VT and ETCO2 were re-equilibrated. In conclusion, capnography serves as simple, bedside method for controlling the adequacy of split ventilation in each patient. No collateral gas flow was observed between the two lungs with different time constants. Ventilator sharing may play a role in emergency situations.

Obesity and diabetes: similar respiratory mechanical but different gas exchange defects.

Diabetes mellitus increases smooth muscle tone and causes tissue remodeling, affecting elastin and collagen. Although the lung is dominated by these elements, diabetes is expected to modify the airway function and respiratory tissue mechanics. Therefore, we characterized the respiratory function in patients with diabetes with and without associated obesity. Mechanically ventilated patients with normal body shapes were divided into the control nondiabetic (n = 73) and diabetic (n = 31) groups. The other two groups included obese patients without diabetes (n = 43) or with diabetes (n = 30). The mechanical properties of the respiratory system were determined by forced oscillation technique. Airway resistance (Raw), tissue damping (G), and tissue elastance (H) were assessed by forced oscillation. Capnography was applied to determine phase 3 slopes and dead space indices. The intrapulmonary shunt fraction (Qs/Qt) and the lung oxygenation index (PaO2/FIO2) were estimated from arterial and central venous blood samples. Compared with the corresponding control groups, diabetes alone increased the Raw (7.6 ± 6 cmH2O.s/l vs. 3.1 ± 1.9 cmH2O.s/l), G (11.7 ± 5.5 cmH2O/l vs. 6.5 ± 2.8 cmH2O/l), and H (31.5 ± 11.8 cmH2O/l vs. 24.2 ± 7.2 cmH2O/l (P < 0.001 for all). Diabetes increased the capnographic phase 3 slope, whereas PaO2/FIO2 or Qs/Qt was not affected. Obesity alone caused similar detrimental changes in respiratory mechanics and alveolar heterogeneity, but these alterations also compromised gas exchange. We conclude that diabetes-induced intrinsic mechanical abnormalities are counterbalanced by hypoxic pulmonary vasoconstriction, which maintained intrapulmonary shunt fraction and oxygenation ability of the lungs.

Diagnostic consideration and bedside estimation of the prognosis in COVID-19 patients / [Diagnosztikus lépések és a betegség prognózisának becslése COVID­19-fertozött betegeken]

In December 2019, a cluster of pneumonia cases of unknown origin occured in Wuhan, China. The identified infective agent is a novel corona virus called "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) and the respiratory disease caused by this agent aquired the name "coronavirus disease 2019" (COVID-19). In March 2020, the World Health Organization (WHO) declared the novel coronavirus outbreak a pandemic. We reviewed the international literature regarding the novel coronavirus outbreak. Here below, we focus mainly on the diagnostic issues of COVID-19 and on the estimation of the prognosis. We detail the relevant anamnestic factors and initial examination results which serve as basics for the clinical suspicion of COVID-19. We also focus on the proper method of microbiological sampling and the relevant informations regarding diagnostic tests like the gold standard real-time reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2. We also cite the current national epidemiologic regulations of testing for novel coronavirus. In the last section, we emphasize the importance and the potential way of early identification of high-risk patients. The COVID-19 pandemic may cause substantial epidemiological and healthcare burden even in Hungary. In addition to the epidemiologic interventions aiming the deceleration of the outbreak, the early identification and the correct hospital treatment remain key issues since these may influence mortality. The chances of the critically ill patients could be improved solely by a high-quality and careful critical care. It is prudent to meet the experiences of colleagues working hard with these patients in the already heavily infected countries. Orv Hetil. 2020; 161(17): 667­671.

Importance of the imaging techniques in the management of COVID-19-infected patients / [A képalkotó diagnosztika jelentosége a COVID­19-fertozött betegek ellátásában]

Critical-care physicians are facing a challenging process in healthcare due to the overwhelming case number of hypoxic respiratory failure patients. Pneumonia has an utmost importance in the primary pathomechanism of the development of critical illness in the COVID-19 patients. Thus, imaging techniques are situated in the frontline to aim the diagnostic decision-making, to follow up the progress and to evaluate the possible complications. Reviewing the available literature, so far the common chest CT, chest X-ray and chest wall ultrasound features are presented, and recommendations are pronounced for the indications of the different modalities. At the initial phase, the atypical presentations of the virus infection are multiplex, peripheral ground glass opacities situated in the right lower lobe of the lung evolving rapidly into a bilateral involvement of the middle and basal zones. Along with the progression, the ratio of the consolidation is increasing subsequently deteriorating into fibrosis with reticular pattern. Chest ultrasound performed at the bedside has a paramount importance to reduce the possible number of health-care worker contacts in consequence of the strict and special infection control orders established on account of the SARS-CoV-2 pandemia. Orv Hetil. 2020; 161(17): 672­677.

The effects of acute blood loss on blood pressure recovery from the Valsalva maneuver.

Human baroreflex regulation plays an important role in stabilising blood pressure. Though we have several indices to quantify cardiovagal responses, sympathetic baroreflex gain remains difficult to assess. We investigated how the recently validated pressure recovery time (PRT) and sympathetic baroreflex gain (SBRS) derived from the Valsalva maneuver was influenced by acute blood loss. 26 healthy blood donors were included in the study (age 35 ± 15 years; 20 men). SBRS was derived from the blood pressure drop (SAP delta) and pressure recovery time during the Valsalva maneuver. Besides we calculated cardiovagal baroreflex parameters, the Valsalva ratio (VR) and a simplified baroreflex gain (VBRS). We compared these parameters before and after the withdrawal of 350-400 ml blood. The baseline systolic blood pressure was the same before and after blood donation (123 ± 17 vs 126 ± 23 mm Hg, NS). The minimum systolic pressure (SAP min) during phase III was significantly lower, and the SAP delta significantly greater after blood withdrawal (SAP min 83 ± 24 mm Hg vs 69 ± 27 mm Hg, p<0.001; SAP delta 41 ± 15 mm Hg vs 57 ± 16 mm Hg, p<0.001). PRT increased significantly (from 2.0 to 3.6s, p<0.006). SBRS did not change between the study conditions (24 ± 12 mm Hg/s vs 22 ± 10 mm Hg/s, NS), nor did the VR and the VBRS: In conclusion, after the acute loss of approximately 350-400 ml blood there was a greater blood pressure drop in phase II and III and a slower blood pressure recovery in phase IV of the Valsalva maneuver that resulted in an unchanged SBRS.

[A simple miracle of water]. / Egyszeru vízi csoda.

Chronic orthostasis intolerance or postural tachycardia syndrome (POTS) is a common problem, which is related to the more severe forms of autonomic neuropathy. Upright posture regularly elicits uncomfortable symptoms in these patients, which impairs their quality of life. We present a typical case, where orthostatic hemodynamic response was significantly improved by ingestion of 500 ml tap water. This simple measure could be a potent, long-term therapeutic tool.

The -509 C/T genotype of TGFbeta1 might contribute to the pathogenesis of benign airway stenosis.

Benign airway stenosis (BAS) is one of the most severe complications of endotracheal intubation. The aim of this pilot study was to compare the frequencies of four polymorphisms of the transforming growth factor (TGF) beta1 gene in patients with BAS due to endotracheal intubation (n = 36) and a control group of intensive care patients who had also undergone endotracheal intubation but did not present BAS (n = 30). One of the studied polymorphisms, the -509 C/T, demonstrated a differential genotype distribution between the affected and the control population: the ratio of heterozygous mutants was significantly (P = 0.0116) higher among the control patients. These data suggest a protective function of the frequent heterozygous C/T genotype against BAS; alternatively, the C/C genotype might be a susceptibility factor for BAS (OR 4.5; 95% CI 1.5123-13.3902). Our findings suggest that, besides other iatrogenic factors, a genetic predisposition might contribute to the pathogenesis of BAS.

Spontaneous baroreflex sensitivity and heart rate turbulence parameters: parallel responses to orthostasis.

Premature ventricular contractions (PVC-s) induce baroreflex mediated arterial pressure and heart rate fluctuations. PVC-related RR interval fluctuations detected on Holter ECG recordings could be characterized by the heart rate turbulence (HRT) parameters, including early post-extrasystolic acceleration, described by turbulence onset, and late deceleration, described by turbulence slope (TS). We have determined the increasing and decreasing spontaneous baroreflex sequence sensitivity (up- and down-BRS) parameters in supine and in upright position in 12 patients with VVI pacemaker while in sinus rhythm. Five-five premature ventricular pacemaker extrastmuli were also applied in both body positions and HRT parameters were calculated. Up- and down-BRS values showed a very close relationship with TS both in the supine (R = 0.94, P < 0.001 and R = 0.92, P < 0.001, respectively), and upright position (R = 0.96, P < 0.001, and R = 0.94, P < 0.001, respectively). The BRS indices decreased significantly upon tilting, which was paralleled by a significant decrease in TS (from 21.6 to 13.9 ms/cycle, P = 0.02). Our findings confirm the close association between TS and spontaneous BRS indices. The relationship is further supported by the similar postural behavior of these parameters. Our results suggest that the confounding effect of posture should be considered when analyzing Holter recordings.