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Игровые аппараты Пин Ап casino на деньги

Nov 2023

Одни из самых первых гаминаторов разрабатывались по обычной схеме – 3 катушки и 9 цепочек. В настоящее время возникли более красочные онлайн казино Pin-up игровые автоматы на деньги с необычным числом цепочек и барабанов. Именно эти слоты обрели отличную репутацию и на данный момент в них делают ставки большинство клиентов азартных клубов

Видео гаминаторы на платформах предельно востребованы. В недавнюю пору ряд игр апгрейднулись. Ни для кого не секрет, что компании онлайн-аппаратов прикладывают множество капитала для развития виртуальных игр. Востребованные виртуальные площадки публикуют щедрые планы для выгоды гостей. Официальный сайт Пин ап казино онлайн на деньги изобрел хитрость для регулярного завлечения посетителей — регулярное обновление выбора машин для ставок.

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На площадке представлены увлекательные гаминаторы от мировых компаний Игрософт, NetEnt, Amatic, Gamomat, Релакс Гейминг, в их аппаратах стоит попробовать Пин ап ставки на деньги и бесплатно. Разработчики придумали игры с выгодными опциями, способствующими заработать целый ряд щедрых выплат. Игровые автоматы Pinup онлайн casino оборудованы хорошей графикой, редкого качества музыкальным оформлением и простым функционалом. Отдельный онлайн-аппарат имеет свою выплату, которая действует на игровой счет. Однако для получения выгоды надо осуществить на сайт casino Pin-up личный кабинет вход.

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На виртуальном веб-ресурсе online casino Pinup Game без проблем можно вращать востребованные симуляторы в тестовом режиме. Это позволит в момент изучить видео-слоты. Парни и девушки могут развлекаться на капиталы. Чтобы это выполнить, нужно легко внести деньги на игровой счет, применяя финансовые сервисы: Skrill, Нетеллер. Некоторые любители азарта применяют платёжную систему Перфект Мани или Pay n Play. Пополнять баланс онлайн казино Пин уп удобно и применяя классические кредитки Visa или MasterCard.

Игры на платформе позволяют обнаружить много нового. Каждый клиент указывает персональную информацию, чтобы администрация могли его распознать. В азартном клубе также ощущаются поощрительные предложения, даже если скачать Пин ап казино. Вступительный приз из щедрых подарков каждый игрок может получить после создания личной страницы. Потом, постоянно клиенты забирают на баланс разные предложения и фриспины.

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Oct 2023

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Wer in einem Casino um echtes Geld spielt, für den ist die Auszahlungsquote ein wichtiger Marker der Gewinnchancen. Sie zeigt dir, wie viel vom Wetteinsatz ein Anbieter wieder an die Spieler ausschüttet. Unsere Bestenliste bietet dir ausschließlich solche, welche die Grenze von 95% locker durchbrechen. Nicht nur bei unserem besten Live Casino, sondern auch bei den anderen Anbietern, brauchst du keine Sorgen haben, falls einmal die Verbindung während des Spielens abbricht. Also ruhig auch den Play Knopf drücken, wenn das Netz schwächer ist, du aber einen guten Lauf hast.

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Der Inhalt von Online-Glücksspielen ist in Deutschland sehr umstritten. Online-Casinos bieten Ihnen mit der Unterstützung von Willkommensbonus und anderen Promotionen viele Gelegenheiten, Geld zu verdienen. Um die sofortige Bonusauszahlung https://brisingr.de.tl/Eragon_Bilder/pic-13.htm#comment zu verhindern, erheben Online-Casinos Wettanforderungen. Für einen vollständigen Überblick über den besten Softwareanbieter schauen Sie sich unsere Liste an. Live Casino-Action wie Roulette oder Dream Catcher sind nicht mehr am Start.

Wichtig war uns dabei, dass die Casinos in Deutschland über ein ausgewogenes Angebot an Spielen verfügen, einen hohen Bonus mit guten Bedingungen bieten und besonders sicher sind. Beste Online Casinos werden mittlerweile staatlich reguliert, um die Sicherheit der Casino Spieler zu gewährleisten. Dafür sorgt der 2021 eingeführte deutsche Glücksspiel-Staatsvertrag.

Alle Online Casinos, die Ihnen unsere Casino Experten empfehlen, sind seriös und sicher. Unsere Experten geben Ihnen alle Informationen dazu, was ein Casino online seriös macht. Also eins muss ich hier mal ganz deutlich hervorheben, der Support ist so freundlich!

In diesem Artikel haben wir unsere Erfahrungen zum Thema deutsche Online Casinos[b] mit dir geteilt. Dabei haben wir viele verschiedene Internet Casinos auf dem Markt unter die Lupe genommen und auf diverse Kriterien geprüft. Um dein erstes Spiel zu starten, musst du dich zunächst auf der Website des Anbieters anmelden. Klick dazu einfach auf der Startseite auf den Button “Registrieren” oder “Anmelden”.

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Oct 2023

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Am häufigsten sind virtuelle Spielautomaten in deutschen Casinos online vertreten. Casinos für Beste Spielautomaten bieten hunderte von Online-Spielautomaten verschiedener Casino-Software-Provider an. In vielen Online Casinos 2023 steht für neue Spieler eine große Anzahl an Casino Zahlungsmethoden zur Verfügung. Besonders, wenn es um die Bonus Angebote und die Auszahlung der Gewinne in Online Casinos in Deutschland geht, erwarten deutsche Spieler reibungslose Abläufe. Ein weiteres Highlight sind die spannenden Turniere bei seriösen Casino-Anbietern.

Die meisten Angebote eines Online Casino Bonus Deutschland unterliegen den Geschäftsbedingungen sowie den zu beachtenden Umsatzbedingungen. Im Folgenden haben wir einige der beliebtesten Boni aufgeführt, die Sie in einem Online Casino in Deutschland finden können. Videopokerspiele sind die idealen Spiele, um die Grundregeln des Pokers ohne großes Risiko zu erlernen, denn Sie spielen nicht gegen andere Spieler, sondern alleine innerhalb der Software. Die Auszahlungsquoten sind hier gewöhnlich sehr gut und Sie können aus zahlreichen Variationen wie Jacks or Better, Deuces Wild, Joker Poker oder All American wählen. Wir bewerten und überprüfen jedes Online Casino auf unserer Auswahlliste. Des Weiteren verwenden wir umfassende Bewertungskriterien, um sicherzustellen, dass wir nur die besten Online-Glücksspielseiten empfehlen.

Bei den besten Online Casinos in Deutschland liegt die Auszahlungsrate im Schnitt bei etwa 96 Prozent, manchmal auch bei 97 Prozent. Wurde ein hoher Jackpot gewonnen, kann diese kurzfristig auf über 100 Prozent steigen. Auch für Low Stakes Spieler stehen die https://forum.fakeidvendors.com/post/7b6nskcn0p Live Casinos echten Spielhallen in nichts nach. Bei den meisten Spielen seid ihr bereits mit wenigen Cents Einsatz mit dabei und könnt euch so langsam rantasten. Neben der Spieleauswahl sollte bei einem Live Dealer Casino auf die Setzlimits geachtet werden.

Diese Fassung des GlüStV sieht vor, dass ab diesem Datum erstmals bundesweit Lizenzen für Online Casinos vergeben werden können. Die zuständige Behörde für die Erteilung der Lizenzen ist das Regierungspräsidium Darmstadt. Durch den GlüStV wird somit eine einheitliche Rechtsgrundlage für legale Online Casinos in Deutschland geschaffen. Es bleibt jedoch abzuwarten, wie sich die neue Gesetzgebung in der Praxis bewährt und ob die Umsetzung der Lizenzen erfolgreich verläuft. Ein Online Casino ist eine Plattform, auf der Nutzer über das Internet Glücksspiele wie beispielsweise Roulette, Poker oder Spielautomaten spielen können. Diese Plattformen sind für Kunden jederzeit und von jedem Ort aus zugänglich, solange eine Internetverbindung vorhanden ist.

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Einzahlungsangebote zählen zu den beliebtesten Formen des Online Casino Bonus. Die besten Online Casinos in Deutschland bieten eine Reihe von Zahlungsoptionen zur Auswahl. Sie können aus sicheren Bankmethoden wie Debitkarten, Kreditkarten, E-Wallets, E-Schecks und mehr wählen. Jedes unserer top Online Casinos hat außerdem niedrige Mindesteinzahlungs- und -auszahlungsbeträge. All diese Casino Spiele werden von namhaften Software Providern angeboten, die eigens darauf spezialisiert sind, Ihnen das beste Spielergebnis zu liefern. Viele Automatenspiele kann man auch kostenlos spielen, im Demo-Modus.

Zwar haben die Befürworter des neuen Glücksspielstaatsvertrages darauf verwiesen,  dass die Legalisierung auch mit Maßnahmen zum Spielerschutz und zur Suchtprävention einhergehen. Allerdings sind diese Maßnahmen bei weitem nicht derart nachhaltig und ausreichend, um der Sucht ernsthaft entgegen zu wirken. Ein monatliches Einzahlungslimit von höchstens 1.000 Euro und eine zentrale Sperrdatei vor. Die Einsätze kann man erst setzen, wenn man vorher eine Einzahlung gemacht hat. Die Einzahlung erfolgt in der Regel per Überweisung, Lastschrift, paysafecard, Kreditkarte etc.

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Ist Locowin legal in Deutschland?

Wie ich während der Recherche für meinen Locowin Test als erstes herausgefunden habe, ist der Betreiber in Besitz einer gültigen Lizenz der Malta Gaming Authority. Hierbei handelt es sich um eine angesehene Zulassung, mit der das Casino legal Glücksspiele in Deutschland anbieten darf.

Januar 2023 – Die GGL (Gemeinsame Glücksspielbehörde der Länder) übernimmt die Regulierung der Online Casinos in Deutschland. Vorher wurde das Online Glücksspiel vom Landesverwaltungsamt Sachsen-Anhalt überwacht. Online Casinos sind preiswerter als Spielbanken, da sie den Spielern häufig Boni oder Freispiele geben, die man in einer traditionellen Spielbank nicht bekommt.

Einschränkungen betreffen geografische Beschränkungen und Steuerverpflichtungen. Eine deutsche Lizenz ermöglicht den Zugang zum deutschen Markt, jedoch mit spezifischen Vorgaben und Einschränkungen, um die Verantwortung im Glücksspiel zu gewährleisten. EU-Lizenzen und andere ausländische Online Casino Lizenzen sind wesentlich für deutsche Online Casinos.

Nicht alle Online Casino Spiele werden gleichermaßen bei den Umsatzbedingungen berücksichtigt. Während die Einsätze bei Spielautomaten in der Regel in voller Höhe zählen, gibt es bei den Tischspielen Einschränkungen. Für Roulette oder Blackjack werden maximal 20% des Umsatzes angerechnet.

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Oct 2023

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Casinos are constructed to be thrilling and entertaining, but each on line casino game is designed so gamers are disadvantaged. Most overseas sites encourage you to provide them a go together with free trials or classes. These are more likely to pay out credit more often than the true video games, giving you a false thought about how typically you’ll be able to win in the true sport. Using today’s technology, it is attainable to gamble virtually anywhere, 24/7.

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Well, there’s tons of how it would work.For example, let’s say I even have $1000 from drug dealing (I don’t!). I deposit it to a web-based casino.You also create an account there. Yes, many real-money online casinos settle for NZD for all funds and wagers, making it simple for Kiwis to fund their accounts, play, and cash out their winnings. The high-value symbol featured is the melon and is used as a wild image, lets cover what games can be found to play.

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While the New Zealand Gambling Commission limits the number of legal casinos out there to gamers, it’s completely legal to gamble at offshore casino websites. All of the casinos that we evaluate are regulated by reputable authorities just like the UK Gambling Commission and Malta Gaming Authority. Additionally, reputable casinos shall be part of GAMSTOP, a self-exclusion scheme that helps gamers to manage their playing habits. Always check that a casino on-line in New Zealand is licensed and controlled earlier than you play to ensure that you are protected and can enjoy a secure and accountable gaming expertise. Many players prefer the convenience of having the ability to entry their favorite on line casino video games when they’re on the go, so you will need to contemplate a casino’s mobile website.

This is the place they ensure an individual who is on a video call is actually who they claim. They may have their RTP (return to player) rates, and payout percentages checked and verified. For an online casino to legally function within New Zealand, it needs to be regulated by the New Zealand Gambling Commission and adjust to the Gambling Act 2003.

Well rest guarantee that for any respected on-line casino, it’s completely safe. Let us start by in search of the most elementary aspect of safety and security at online casinos – the license. The very best and safest on-line casinos will typically all function the identical security hallmarks. Many respectable sports betting web sites have a quantity of issues that make them reliable. But sadly, with the rise in love for sports betting, there are numerous hoaxes in the business too.

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Sep 2023

Задумки об гаминаторах появляются у большинства пользователей. Кое-какие посетители думают, что ставить деньги в азартных играх – логично. Ведь с помощью ставок можно почувствовать необыкновенные эмоции в онлайн-слотах. Главный сайт Пинап Украина можно отлично выиграть денег на развлечениях. Множители в карточных играх, в основном, от 2.3 до 3.6. Это дает возможность игрокам устанавливать ставки, фактически не смотря на коэффициенты.

Среди распространенных пояснений, из-за чего же гости играют в онлайн-игры – «непринужденное времяпровождение». Еще 1000 лет назад карточные игрушки предоставляли юзерам уйму чувств, а с развитием гаджетов, онлайн область стала другой.

В online casino стали появляться необычные игровые автоматы Pin-up 24, разнообразные бонусные сектора, а также вышло на свет большое количество new аппаратов. Прямо сегодня большой части игроков увлекательно делать прогнозы в прикольных игрушках, невзирая на то, что фактор вероятного фейла также может быть. Более 100 геймеров регулярно в онлайн-казино устанавливает ставку в разных slots от оператора Ваздан. Ведь и вправду, так почему и не поиграть в азартные игрушки, где есть пошлая тематика, большое количество разработанных состязаний и огромное число подарков? Также людям по вкусу и слот-модели от ИГТ. В них игроки могут прочувствовать действительно прикольную картинку, в числе востребованных видеослотов: Double Diamond, Texas Tea, Chostbusters. Часть посетителей заявляет о таких преимуществах:

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Сейчас юзеры смело переходят на главный сайт Пинап Украина используя Айос и Андроид гаджеты. Гости утверждают, что клуб предоставляет время расслабиться, хоть и иногда это дорого. Большая часть из ребят делают прогнозы даже на $50 и срывают крупные джекпоты.

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Aug 2023

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Your best bet is to rely on the information provided by industry professionals who are involved in the evaluation and ranking of the most trusted Philippine casinos and gambling sites. They are trained to analyze online casino businesses and determine their legitimacy, quality and value to players. Filipino players can legally participate in online casino entertainment as long as the destination at which they are playing is located and regulated outside of the Philippines. The Filipino gambling laws do not prohibit players from participating in legally licensed and regulated offshore Internet gambling.

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You can take a shortcut and pick a place to play from a list of preselected, vetted sites. GCash is picking up momentum as online gamblers are looking everywhere for reliable online payment services to fund their gambling accounts. The operator promises no hidden fees and secure transfers to online gambling sites in the Philippines. Who wouldn’t want to play casino games online in the Philippines with a sizeable welcome bonus? Looking at the best Philippine casino bonuses we have to admit that they are compelling – to say the least.

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Given various amazing promotion offers, you have much higher chance to win big! However, the dreams coming true won’t happen if you just sit there and do nothing. Betvisa gives you the best online live betting experience with live streaming of football, horse racing, boxing, tennis and more. Betvisa Philippines delivers what is most important to gamers – innovation and convenience. We provide a simple, fast and convenient way to place your sports bets online.

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Letters to Editor

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Reply to: Extracorporeal membrane oxygenation transport for severe COVID-19 – why we can and should!

Dec 2022

Journal: American Journal of Respiratory and Critical Care Medicine
PMID: 35882061

Scientific Presentations

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Bougie Trial Results

Dec 2022

Scientific Presentations

Posted on

Pilot Trial Results

Dec 2022

Scientific Presentations

Posted on

Prepare II

Dec 2022

Review Articles

Posted on

Intravenous fluid therapy in sepsis.

Oct 2022

Journal: Nutrition in Clinical Practice
PMID: 35801708

Past Trials

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BOUGIE Trial

Oct 2022

Importance: For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer (“bougie”) increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain.

Objective: To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt.

Design, setting, and participants: The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021.

Interventions: Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546).

Main outcomes and measures: The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%.

Results: Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group.

Conclusions and relevance: Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet.

Trial registration: ClinicalTrials.gov Identifier: NCT03928925.

Past Trials

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CHECK-Up Trial: Up

Oct 2022

Background: Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room.

Methods: Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts.

Results: The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position (P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively.

Conclusions: In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation.

Trial registry: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Keywords: endotracheal intubation; hypoxemia; randomized trial.

Manuscript Title: “A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults.”

Journal: Chest

PMID: 28487139

Past Trials

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PreVent Trial

Oct 2022

Background: Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial.

Methods: In a multicenter, randomized trial conducted in seven intensive care units in the United States, we randomly assigned adults undergoing tracheal intubation to receive either ventilation with a bag-mask device or no ventilation between induction and laryngoscopy. The primary outcome was the lowest oxygen saturation observed during the interval between induction and 2 minutes after tracheal intubation. The secondary outcome was the incidence of severe hypoxemia, defined as an oxygen saturation of less than 80%.

Results: Among the 401 patients enrolled, the median lowest oxygen saturation was 96% (interquartile range, 87 to 99) in the bag-mask ventilation group and 93% (interquartile range, 81 to 99) in the no-ventilation group (P = 0.01). A total of 21 patients (10.9%) in the bag-mask ventilation group had severe hypoxemia, as compared with 45 patients (22.8%) in the no-ventilation group (relative risk, 0.48; 95% confidence interval [CI], 0.30 to 0.77). Operator-reported aspiration occurred during 2.5% of intubations in the bag-mask ventilation group and during 4.0% in the no-ventilation group (P = 0.41). The incidence of new opacity on chest radiography in the 48 hours after tracheal intubation was 16.4% and 14.8%, respectively (P = 0.73).

Conclusions: Among critically ill adults undergoing tracheal intubation, patients receiving bag-mask ventilation had higher oxygen saturations and a lower incidence of severe hypoxemia than those receiving no ventilation. (Funded by Vanderbilt Institute for Clinical and Translational Research and others; PreVent ClinicalTrials.gov number, NCT03026322.).

Manuscript Title: “Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults.”

Journal: New England Journal of Medicine

PMID: 30779528

Systems based practice

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ICU Survivor Clinic Trial

Oct 2022

Objectives: To examine the effect of an interdisciplinary ICU recovery program on process measures and clinical outcomes.

Design: A prospective, single-center, randomized pilot trial.

Setting: Academic, tertiary-care medical center.

Patients: Adult patients admitted to the medical ICU for at least 48 hours with a predicted risk of 30-day same-hospital readmission of at least 15%.

Interventions: Patients randomized to the ICU recovery program group were offered a structured 10-intervention program, including an inpatient visit by a nurse practitioner, an informational pamphlet, a 24 hours a day, 7 days a week phone number for the recovery team, and an outpatient ICU recovery clinic visit with a critical care physician, nurse practitioner, pharmacist, psychologist, and case manager. For patients randomized to the usual care group, all aspects of care were determined by treating clinicians.

Measurements and main results: Among the primary analysis of enrolled patients who survived to hospital discharge, patients randomized to the ICU recovery program (n = 111) and usual care (n = 121) were similar at baseline. Patients in the ICU recovery program group received a median of two interventions compared with one intervention in the usual care group (p < 0.001). A total of 16 patients (14.4%) in the ICU recovery program group and 26 patients (21.5%) in the usual care group were readmitted to the study hospital within 30 days of discharge (p = 0.16). For these patients, the median time to readmission was 21.5 days (interquartile range, 11.5-26.2 d) in the ICU recovery program group and 7 days (interquartile range, 4-21.2 d) in the usual care group (p = 0.03). Four patients (3.6%) in the ICU recovery program and 14 patients (11.6%) in the usual care group were readmitted within 7 days of hospital discharge (p = 0.02). The composite outcome of death or readmission within 30 days of hospital discharge occurred in 20 patients (18%) in the ICU recovery program group and 36 patients (29.8%) in usual care group (p = 0.04).

Conclusions: This randomized pilot trial found that a multidisciplinary ICU recovery program could deliver more interventions for post ICU recovery than usual care. The finding of longer time-to-readmission with an ICU recovery program should be examined in future trials.

Manuscript Title: “Randomized Clinical Trial of an ICU Recovery Pilot Program for Survivors of Critical Illness.”

Journal: Critical Care Medicine

PMID: 31385881

Past Trials

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BALANCE Trial

Oct 2022

Rationale: The feasibility and clinical outcomes of conservative fluid management after sepsis resuscitation remain unknown.

Objectives: To evaluate the effect of a conservative fluid management protocol on fluid balance and intensive care unit (ICU)-free days among patients with sepsis.

Methods: In a single-center phase II/III randomized trial, we enrolled adults with suspected infection, ≥2 systemic inflammatory response syndrome criteria, and either shock (mean arterial pressure <60 mm Hg or vasopressors) or respiratory insufficiency (mechanical ventilation or oxygen saturation <97% and fraction of inspired oxygen ≥0.3). Patients were randomized 1:1 to usual care or a conservative fluid management protocol. The protocol restricted intravenous fluid administration during shock to treatment of oliguria or increasing vasopressor requirement. In the absence of shock, loop diuretic infusion targeted equal fluid input and output each study day. The primary outcomes were mean daily fluid balance (phase II) and ICU-free days (phase III).

Results: At the completion of phase II (n = 30), the difference in mean daily fluid balance between groups (-398 mL) was less than the prespecified threshold (-500 mL) and the trial was stopped. Patients in the conservative fluid management (n = 15) and usual care (n = 15) groups experienced similar cumulative fluid input (8450 mL vs 7049 mL; P = .90) of which only 14% was intravenous crystalloid or colloid. Loop diuretic infusion occurred more frequently in the conservative fluid management group (40% vs 0%; P = .02), and cumulative fluid output was 10 645 mL in the conservative fluid management group compared to 6286 mL in the usual care group (P = .39). Hemodynamic, respiratory, and renal function did not differ between the groups.

Conclusions: In this phase II trial, a conservative fluid management protocol did not decrease mean daily fluid balance by more than 500 mL among patients with sepsis.

Registration: Clinicaltrials.gov; NCT02159079.

Keywords: acute kidney injury; intravenous fluid; sepsis.

Conflict of interest statement

CONFLICTS OF INTEREST

All authors completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declared no potential conflicts of interest with the current work. W.H.S. reported serving on advisory boards for Venaxis, Inc., Ferring Pharmaceuticals, and Cempra Pharmaceuticals, and as a consultant for Abbott Point-of-Care. T.W.R. reported serving on an advisory board for Avisa Pharma, LLC and as the Director of Medical Affairs for Cumberland Pharmaceuticals, Inc.

Manuscript Title: “Conservative Fluid Management After Sepsis Resuscitation: A Pilot Randomized Trial.”

Journal: Journal of Intensive Care Medicine

PMID: 30630380

Past Trials

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PREPAREII Trial

Oct 2022

Importance: Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain.

Objective: To determine the effect of fluid bolus administration on the incidence of severe hypotension, cardiac arrest, and death.

Design, setting, and participants: This randomized clinical trial enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation at 11 intensive care units in the US between February 1, 2019, and May 24, 2021. The date of final follow-up was June 21, 2021.

Interventions: Patients were randomly assigned to receive either a 500-mL intravenous fluid bolus (n = 538) or no fluid bolus (n = 527).

Main outcomes and measures: The primary outcome was cardiovascular collapse (defined as new or increased receipt of vasopressors or a systolic blood pressure <65 mm Hg between induction of anesthesia and 2 minutes after tracheal intubation, or cardiac arrest or death between induction of anesthesia and 1 hour after tracheal intubation). The secondary outcome was the incidence of death prior to day 28, which was censored at hospital discharge.

Results: Among 1067 patients randomized, 1065 (99.8%) completed the trial and were included in the primary analysis (median age, 62 years [IQR, 51-70 years]; 42.1% were women). Cardiovascular collapse occurred in 113 patients (21.0%) in the fluid bolus group and in 96 patients (18.2%) in the no fluid bolus group (absolute difference, 2.8% [95% CI, -2.2% to 7.7%]; P = .25). New or increased receipt of vasopressors occurred in 20.6% of patients in the fluid bolus group compared with 17.6% of patients in the no fluid bolus group, a systolic blood pressure of less than 65 mm Hg occurred in 3.9% vs 4.2%, respectively, cardiac arrest occurred in 1.7% vs 1.5%, and death occurred in 0.7% vs 0.6%. Death prior to day 28 (censored at hospital discharge) occurred in 218 patients (40.5%) in the fluid bolus group compared with 223 patients (42.3%) in the no fluid bolus group (absolute difference, -1.8% [95% CI, -7.9% to 4.3%]; P = .55).

Conclusions and relevance: Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse.

Manuscript Title: “Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial”

Past Trials

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SMART Trial

Oct 2022

Background: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.

Methods: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days – a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) – all censored at hospital discharge or 30 days, whichever occurred first.

Results: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).

Conclusions: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).

Manuscript Title: “Balanced Crystalloids versus Saline in Critically Ill Adults.”

Journal: New England Journal of Medicine

PMID: 29485925

Past Trials

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SALT-ED Trial

Oct 2022

Background: Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU).

Methods: We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days – a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) – all censored at hospital discharge or 30 days, whichever occurred first.

Results: A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P=0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P=0.01).

Conclusions: Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SALT-ED ClinicalTrials.gov number, NCT02614040 .).

Conflict of interest statement

Dr. Self reports receiving advisory board fees from Venaxis, Cempra Pharmaceuticals, Ferring Pharmaceuticals, and Biotest, consulting fees from Abbott Point of Care, and travel support from Gilead Sciences; and Dr. Rice, receiving consulting fees from Cumberland Pharmaceuticals and Avisa Pharma. No other potential conflict of interest relevant to this article was reported.

Manuscript Title: “Balanced Crystalloids versus Saline in Noncritically Ill Adults.”

Journal: New England Journal of Medicine

PMID: 29485926

Past Trials

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CHECK-Up Trial: Checklist

Oct 2022

Background: Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation.

Methods: A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation.

Results: The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79-98) in the checklist group vs 93% (IQR, 84-100) with usual care (P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94-133) in the checklist group vs 108 mm Hg (IQR, 90-132) in the usual care group (P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life-threatening procedural complications (40.8% vs 32.6%; P = .20).

Conclusions: The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care.

Trial registry: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Keywords: adult; airway management; checklist; critical care; endotracheal; intubation; ventilation.

Manuscript Title: “A Multicenter Randomized Trial of a Checklist for Endotracheal Intubation of Critically Ill Adults.”

Journal: Chest

PMID: 28917549

Past Trials

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SALT Trial

Oct 2022

Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.

Objectives: To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.

Methods: This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction.

Measurements and main results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98).

Conclusions: An electronic health record-embedded, cluster-randomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt. Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

Trial registration: ClinicalTrials.gov NCT02345486.

Keywords: acute kidney injury; critical illness; crystalloid; intravenous fluid; saline.

Manuscript Title: “Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial.”

Journal: American Journal of Respiratory and Critical Care Medicine

PMID: 27749094

Past Trials

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FELLOW Trial: VL/DL

Oct 2022

Objective: To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults.

Design: A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows.

Setting: Medical ICU in a tertiary, academic medical center.

Patients: Critically ill patients 18 years old or older.

Interventions: Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation.

Measurements and main results: Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator’s previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95% CI, 0.82-5.02, p = 0.12). Secondary outcomes of time to intubation, lowest arterial oxygen saturation, complications, and in-hospital mortality were not different between video and direct laryngoscopy.

Conclusions: In critically ill adults undergoing endotracheal intubation, video laryngoscopy improves glottic visualization but does not appear to increase procedural success or decrease complications.

Manuscript Title: “Randomized Trial of Video Laryngoscopy for Endotracheal Intubation of Critically Ill Adults.”

Journal: Critical Care Medicine

PMID: 27355526

Past Trials

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FELLOW Trial: AO

Oct 2022

Rationale: Hypoxemia is common during endotracheal intubation of critically ill patients and may predispose to cardiac arrest and death. Administration of supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent hypoxemia.

Objectives: To determine if apneic oxygenation increases the lowest arterial oxygen saturation experienced by patients undergoing endotracheal intubation in the intensive care unit.

Methods: This was a randomized, open-label, pragmatic trial in which 150 adults undergoing endotracheal intubation in a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no supplemental oxygen during laryngoscopy (usual care). The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after completion of endotracheal intubation.

Measurements and main results: Median lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with usual care (95% confidence interval for the difference, -1.6 to 7.4%; P = 0.16). There was no difference between apneic oxygenation and usual care in incidence of oxygen saturation less than 90% (44.7 vs. 47.2%; P = 0.87), oxygen saturation less than 80% (15.8 vs. 25.0%; P = 0.22), or decrease in oxygen saturation greater than 3% (53.9 vs. 55.6%; P = 0.87). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality were similar between study groups.

Conclusions: Apneic oxygenation does not seem to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared with usual care. These findings do not support routine use of apneic oxygenation during endotracheal intubation of critically ill adults. Clinical trial registered with www.clinicaltrials.gov (NCT 02051816).

Manuscript Title: “Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill.”

Journal: American Journal of Respiratory and Critical Care Medicine

PMID: 27355526