Richard Fleischer

Cristelle Maury

"To Better Tracks and Steadier Nerves": The Role of the Train in the Representation of Masculinity in The Narrow Margin (

In many ways, the phrase "To better tracks and steadier nerves"proffered to Detective Walter Brown (Charles McGraw) by Ann Sinclair (Jacqueline White)sums up the renewed representation of the male protagonist as a complex noir antihero. In The Narrow Margin, Sinclair is a benevolent, upper-class mother and an unobtrusive train passenger who turns out to be the widow of a mobster. Brown is a police detective in charge of escorting Frankie Neal, a "gangster moll" (Mary Windsor), on the same train from Chicago to Los Angeles, where she is to testify before a grand jury against her late husband's associates. Neal is, of course, but a decoy for the real widow, Sinclair. Brown's efforts to protect the slain gangster's wife against the mobsters out to get her, puts him in an apparently dominant position. However, he also has to face a series of setbacks which befits his precarious status as a hero, especially when it becomes clear that he has been used as a pawn, since he ignored that the "widow" was in fact an undercover police officer. Brown finds out that the home office has been testing him, because he was suspected of taking bribes, and he ultimately turns out a classical film noir anti-hero on two accounts: he is manipulated and wrongly accused.

In keeping with a long line of film noir detectives who are characterized by their problematic relationship with law enforcement, Brown can also be defined by his ambivalence. 1 He hesitates between righteousness and corruption. Indeed, one of the central elements of the plot is the fact that he is torn between good and evil, as he is tempted by bribes. Wavering between excessive manliness and the lack of it, the male * To cite this article:

filmjournal.org filmjournal.sercia@gmail.com protagonist is alternately represented as a very self-confident cop or a disempowered antihero. Like other film noir protagonists, Brown is characterized by his ambivalence and his inner contradictions. Classical though these notions might be, they are given new expression in The Narrow Margin as the train renders the traditional representation of the noir detective as an antihero more complex and his contradictions more dramatic. As Mark Seltzer explains, the railway system has the ability at once to enhance and constrict human action:

[…] the railway system combines mobility and incarceration, confining still or stilled bodies in moving machines directed by mechanical prime movers. The railway, like the elevator […] puts stilled bodies in motion. What these mobile technologies make possible, in different forms, are the thrill and panic of agency at once extended and suspended.

The train extends space and allows for faster spatial movement while paradoxically keeping the body still in an enclosed space. Hence, it concurrently extends the limits of the human body while confining it in an enclosed space.

By using the trope of the train, this film participates in the transformation of the genre at work in late films noirs. As Foster Hirsch explains in his comprehensive study of film noir, "[i]n the fifties noir […] began to tamper with generic elements that had become traditional. Some of these variations extended the life of the genre." 3 Although The Narrow Margin is not the first film noir to utilize the visual and aural possibilities of trains, it exploits this traditional noir setting in a way that renews tough guy masculinity, one of the classical subjects of film noir, and the genre's complex representation of the male protagonist as an ambiguous and ambivalent hero.

The train creates confusion between the human element and the machine, and thereby renews the themes of moral ambivalence and duality of the male protagonist. This article is concerned with exploring the contradictory effects of mechanization on the hero's actions to see how they modify the depiction of the classical film noir detective. Moreover, as "the mechanical double of cinema,"4 the train draws attention to the camera, and thereby to the artificiality of film noir conventions and codes. Clearly, in this film "railway language […] works as a metalanguage for cinematography." These metafictional devices shed new light on the characterization of the film noir protagonist as an antihero. In fact, the ambivalence of the male protagonist, as well as his dual status as a superman and anti-hero, echoes contemporaneous debates on the changing status of men in the 1950s, the so-called "Cold War anxieties" shaped by concerns about gender, sexuality and the male itself.

Human enhancement: a Super Hero?

During most of the film, Brown is represented as an overly self-confident cop, in charge of the action. He displays all the skills of a good detective: physical strength, professionalism, quick decision-making, self-confidence, absence of hesitation, and a strong filmjournal.org filmjournal.sercia@gmail.com sense of authority. In short, he possesses all the qualities of Hollywood's "official heroes" 5 namely, "the best attributes of adulthood: sound reasoning and judgment, wisdom and sympathy based on experience". "Willing to undertake even those public duties demanding personal sacrifice," 6 he has a lot in common with Chandler's "ideal hero," 7 and also follows in the footsteps of the prototypical western hero in charge of escorting a prisoner from one place to another.

The train plays an important part in enhancing and extending Brown's physical capabilities. He seems to absorb the visual and aural energy of the train, as a series of parallels between his behaviour and the train's manifestations indicate. For example, at Chicago's Grand Central Station, shortly before the train's departure, the soundtrack is composed of a series of rattling, whistling and chugging sounds that stop as soon as Brown boards the stationary train. This makes perfect sense at the diegetic level: Brown has entered the train, and the noises of the platform can no longer be heard once he is inside the train. However, these noises are replaced by the sound of his coarse voice as he addresses Mrs. Neal. This creates a kind of continuity between mechanic and organic sounds. Throughout the film, his regular outbursts of anger when he addresses either the gangsters or Neal, are echoed and amplified by the rattling sound of the locomotive.

Visually, parallels between his physique and the locomotive are established by transitions with shots of the locomotive. For example, his conversation with Mrs. Neal, in which he displays self-confidence and a strong sense of authority, cuts to a shot of the locomotive:

Neal: I'm in a spot, Brown, and it's your job to protect me. It's your move. Brown: You're wrong, it's his [the gangster's]. We're going to let him make it, Mrs. Neal.

In this scene, the verbal exchange establishes him as a manly man. It indicates that he knows everything, and is capable of making quick decisions, without hesitating 8 . Conversely, Neal claims her need for protection, and puts her fate in Brown's hands in one of these stereotypical "interpersonal rituals" described by sociologist Erving Goffman as conveying "the belief (in Western society) […] that women are precious, ornamental, and fragile, uninstructed in, and ill-suited for anything requiring muscular exertion or mechanical or electrical training or physical risk." 9 This exchange ends with a shot of the locomotive, racing along the straight tracks, unhampered by the horizontal iron railings that frame the screen and seem to block the way. Instead of slowing down, the locomotive lets off steam to cover the railings and races along (fig. 1). This transition establishes a parallel between 5 Robert Ray, A Certain Tendency of the American Cinema, 1930-1980 Brown and the locomotive that reinforces his strong verbal domination. It is almost as if the locomotive transferred its steam energy onto Brown, providing an apt metaphor for sexual intercourse, thereby reinforcing his sexual potency, and heightening his manliness.

In the same way, Brown is endowed with the driving force of the machine when he enters into a fight with one of the gangsters. As a primitive form of masculine testing, fighting is the opportunity for the detective to display his manliness. Fighting scenes are almost a prerequisite of film noir. 10 Frank Krutnik noted that "the boxing-scenes themselves often serv[ed] to present a stark spectacle of masculine triumph and defeat. The ring becomes an enclosed arena of masculine performance." 11 This is precisely the case here. The jolts of the train amplify the blows that Brown strikes and are instrumental in his victory. It seems that the energy required for the train to maintain its speed propagates to his muscles and his flesh, and creates a correspondence between man and machine. In a way, Brown benefits from the technological enhancement of "auxiliary organs" mentioned by Freud in his description of the "technological man":

Man has, as it were, become a kind of prosthetic God. When he puts on all his auxiliary organs he is truly magnificent; but those organs have not grown on to him and they still give him much trouble at times.

In that regard, he is a kind of superman, or an ideal hero. However, substituting a machine for human strength minimizes the importance of physical abilities. This is what might give him "much trouble at times". Indeed, the consequence of victory at the hands of the machine is that it also casts doubt on the efficiency of his actions, illustrating Seltzer's remark that "the uncertain status of the principle of locomotion precipitates the melodramas of uncertain agency." 13 In other words, neither the characters nor the audience are sure whether it is the machine or the human who has won the fight. The identity of the real agent remains unclear.

Moreover, Brown expertly uses the reflection provided by the window of a train passing in the other direction to kill Densel (Peter Virgo) by an adroitly triangulated shot through the door of a railroad car. This very unlikely shot that allows him to save Mrs. Sinclair who was held hostage turns him, albeit temporarily, into a superhero. He owes his victory as much to his personal fighting skills as to the motive power of the train.

Constriction, Control and Fusion: A Disempowered Hero in the "machine culture" 14

At the same time as he is "augmented", Brown is also disempowered by the movements of the machine. The train works as a visual motif of entrapment. As one of the classical film noir locales it provides a "tight, confined space […] from which there is no escape." 15 The characters move through narrow corridors; they are seen sitting or standing in stuffy compartments, walking through multiple doors. The lack of space is further reinforced by the use of close shots and two-shots. Classical high-and low-angle shots and light effects -shadows and chiaroscuro -create a sense of claustrophobia and oppression. The fight sequence illustrates this characteristic treatment of space and suggests that Brown is submitted to the spatial constraints of the train. The cinematography highlights the impression of confinement, or even of incarceration: as the fight intensifies, and as the two fighters occupy more and more space, the scale of the shots shifts from medium to close shots, while a hand-held camera and high-angle and low-angle shots are used to save floor space. A close-up of the two men wrestling on the floor, shot from behind the pipe of the washbasin (fig. 2), increases this impression of entrapment. Visual entrapment is used to express the male protagonist's The train also seems to contain narrative power and exert narrative control, as the plot follows the course of the railway journey. It starts when the characters board the train in Chicago and ends when the train reaches its final destination, once the gangsters have been arrested, and the widow has arrived safe and sound. As the train dashes along the tracks, unhampered, it seems to deprive Brown of his control over the course of events. His tribulations and hesitations are dependent on the direction taken by the train. The spatiotemporal constrictions of the train seem to prevail over the extensions of the body, giving the train, so to speak "the upper hand". Motion and volition being no longer connected, the male character is disempowered by the machine in motion.

Moreover, the links between the train and the male protagonist point to a confusion between organic and mechanical systems that redraw "the uncertain and shifting line between the natural and the technological in machine culture and also the ways in which such shifts in the traffic between the natural and the technological make for the vicissitudes of agency." 16 This blurring of boundaries announces the prominence given to machines. It is aptly noted by Mrs. Sinclair when she comments that Brown behaves like a machine: "Maybe you're like the train. When it's moving everything is a blur. When it slows down and stops, you begin to notice the scenery." The aural and visual channels of expression further this confusion.

The soundtrack is characterized by the absence of extradiegetic music and the omnipresence of the intradiegetic sounds of the train. These sounds create dramatic and aesthetic effects that enhance the visual drama. Although the whistling, rattling or puffing of the train should be nothing more than mere background noises, or sound effects subjected to the impression of reality, they provide here a kind of emotional orchestration. For example, in the fight sequence, the continuous sound of the wheels on the tracks matches the rhythm of the heavy panting of the two men, thus having a double effect: that of personifying the train and reifying the fighters.

The editing also points to confusion between humans and machines. In one of the transitions, a shot of Windsor filing her nails dissolves into a shot of the train's wheels, while the sound of the nails on the file turns into the sound of the wheels on the tracks. These overlapping shots and sounds fuse together human and mechanical movements, and illustrate how the film "couples the body and the machine." 17 While the train is endowed with anthropomorphic attributes, the bodies are subjected to an alteration that seems "to filmjournal.org filmjournal.sercia@gmail.com be actuated by a mechanical logic that defies conscious choice." 18 As the train is, so to speak, gaining momentum, the characters, on the other hand, and particularly Brown, tend to become more passive. The reversal of roles bestows volition on the train and deprives the characters of their agency, and this inversion of the natural order of things has not only a disempowering function as shown earlier but also a dehumanizing effect.

The prominence given to the train also works for the camera. The association between the two machines is foregrounded in the opening sequence, where a series of swift tracking shots of a train establish both the mobility of the locomotive and the conspicuous presence of the camera. The trajectories taken by the train and by the camera follow opposite directions. The absence of human beings either controlling the train or looking at it suggests that the locomotive and the camera are, in a sense, endowed with wills of their own. The opposing forces of the filmographic movements -the movements of the camera -and the profilmic movements -the movements of the train placed in front of the camera -create a tension that relegates the characters to a position of secondary importance and establishes the reign of the machines: that of the locomotive in the first place -as the train is set up as the ruling force of the film -but also that of the camera, as its mobility cannot be accounted for merely by human presence or activity.

These multiple parallels established between the train and the camera not only blur the boundaries between organic and mechanical elements, instituting the reign of the machines, but also hint at a metafictional interpretation. They draw attention to the artificiality of the diegetic world, when, for example, the length of the story coincides with the time it takes for the train to reach its destination. They also point to the fact that characters are not made of flesh and blood, but are the products of multiple mechanical artifices inherent in filmmaking. The shooting and editing phases as well as the process of adding the soundtrack are rendered visible to draw attention to film noir codes and conventions, and more specifically to the conventional representation of gender roles.

Metafictional Intent

The film teems with metafictional devices that remind the spectators that they are watching a film. One of the main devices is the visual establishment of parallels between the camera and the train. Indeed, the "mechanization of film noir" made possible by the introduction of a train as the driving force of the plot is suggested through the conspicuous presence of the camera.

To begin with, the train itself works as a direct reference to the camera, since the cinema and the locomotive are, after all, two inventions dating from the industrial revolution. The similarities are striking: first in the soundtrack, with the incessant background noise of the train, akin to the rattling sound made by the first projectors and cameras, and secondly in the visual style, with the dark corridors and compartments lit by flickering lights, similar to the lights in a projection booth. As Wim Wenders has noted, 19 trains, cameras and projectors use the same material and technology: they are all made of wheels, axles, connecting rods and reels. They are still objects that create movement; they filmjournal.org filmjournal.sercia@gmail.com have the effect of increasing and amplifying human beings' physical, perceptual and conceptual capacities. Moreover, a camera and a train both take spectators and travellers from one point to another. The spectator of a film in a movie theatre is placed in the same position as a traveller on a train, who would be watching the passing landscape, enjoying a long magnificent tracking shot. 20 Then, the "plastic signs"21 of the image -that is to say all the signifiers including colors, light, texture and form -evoke the equipment needed for the shooting of a film. The squares and rectangles formed by the windows look like a celluloid film passing through the projector (see fig. 4) and the white posts placed along the railway tracks look like the perforations on the edges of a film strip. As the train is slowing down, the filmstrip even becomes perceptible, highlighting the similarities between the train and a projector (see fig. 5). The rivets driven into the train's body recall the small perforations on both sides of the filmstrip. This type of shot taken from the inside of the train recurs so as to create a motif. Finally, the scene in which Brown uses a highly sophisticated scheme to save Sinclair's life has an interesting composition that draws attention to the mise en abime of framing. Beyond the diegetic motives, this arrangement highlights the techniques necessary for the creation of such cinematographic effects, while distancing the main point made in the sequence, namely, the fact that Brown has recovered his agency and his manliness. In his study of the scene, Alain Masson notes that the cinematographic effect is plainly visible, and intentionally so:

filmjournal.org filmjournal.sercia@gmail.com
The sequence is highly improbable, not only because of the miraculous presence of the other train, but also because of the camera setup: McGraw turns left to see the reflection of the people who are to his right! The coincidence is thus a mere cinematographic effect that no one attempts to conceal.

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Besides the visual hints of metafiction, the film also contains self-reflexive dialogues. For example, Brown mentions the iconography of classical 1930s gangster movies to prove that the gangster's widow is going to have all the attributes of a "gangster moll" as his conversation with Forbes on their way to pick her up shows: Forbes ironically points out that Brown is prejudiced. The latter's conviction that she will be "cheap, flashy, strictly poison" as he later adds, almost sounds like a catchphrase from a classical 1930s gangster movie. His opinion ultimately reduces her to the status of object. Likewise, his interactions with Neal, who behaves like a gangster moll, are mostly based on perfunctory stimuli and blunt responses. He reacts exactly in the same way every time she does or says something predictable: he yells at her commonplace, prejudiced statements, implying that she is an unscrupulous woman of easy virtue. Neal's retort ironically alludes to the chivalric attitude of the private detective described by Raymond Chandler in his 1944 definition of the "ideal hero,"23 which obviously no longer applies to Brown.

Neal: How long will my luck last? Brown: As long as there are cops like Forbes around to get killed for you. Neal: Like you, I suppose. Brown: Yeah, like me. Neal: Well, my taste doesn't usually run to cops, but you might not be such dull company at that. Brown: Mrs. Neal, we better get one thing straight. You're just a job to me. A COD24 package to be delivered to the LA grand jury... and there's no joy in it. I don't like you any more than Forbes did, but he got himself murdered for you... and maybe I will, too. That's what they pay me for. Do we understand each other? Neal: Relax, Percy, your shield's untarnished. I've changed my mind.

This self-conscious dialogue about the codes of classical gangster movies and hard-boiled fiction turns them into stock characters. For Hirsch, "her dialogue sounds like a parody of the hard-boiled school and the exaggeration is a tip off that noir conventions are being burlesqued."25 Kinesics reinforces the self-consciousness of the dialogue. As they confront their arguments, the two characters alternately move their heads forward and backward (figure 6). They look like two puppets in a Punch-and-Judy show. It is as if the rhythmic movements of the train had contaminated them. Such sparring matches evoke "something mechanical encrusted upon the living"26 and hint at the extrafilmic reality of two actors performing roles, distancing and almost parodying the traditional gender roles that are staged in their interactions.

filmjournal.org filmjournal.sercia@gmail.com All in all, the metafictional devices used in the dialogues, in the acting, and in the visual channel of expression have the effect of turning the characters into objects of study. They allow for metafictional comments on the film as a film, but also on film noir as a genre and on the performative aspects of gender roles. As Thomas Schatz points out, generic evolution entails "patterns of increasing self-consciousness":

As a genre's classic conventions are refined and eventually parodied and subverted, its transparency gradually gives way to opacity: we no longer look through the form (or perhaps "into the mirror") to glimpse an idealized self-image, rather we look at the form itself to examine and appreciate its structure and its cultural appeal.

27

Even though film noir was not established as a genre until the 1960s, it clearly contains most of the ingredients of the films later included in this film cycle. The Narrow Margin was released during what Paul Schrader retrospectively named "the third and final phase of film noir 1949-53." 28 It contains metafictional comments expressed through the parallels between the train and the camera, and through characters shown as performing roles. Mary Windsor plays the role of an undercover police officer playing the role of a gangster moll, a character that had long vanished from the screens in 1952. Charles McGraw's attempt at playing the part of an incorruptible cop, with Chandleresque, chivalric overtones appears somehow outmoded. These anachronistic characters who overplay gender differences and who perform their roles in a very mechanical style, reveal that gender is a role that one plays.

The introduction of metafictional distancing of gender roles, as well as the parallels established between the male protagonist, and the train are interesting for a film that was released at a time when the lack of virility was seen as the root cause of many social and political issues. Film noir has often been analysed as reflecting the anxieties about changing masculinity in the postwar and cold war eras. We have seen that in this film, the train endows the hero with extraordinary powers as much as it disempowers him. In doing so, the train helps to modify the representation of masculinity.

The Train as a Political Metaphor

27 Thomas Schatz, Hollywood Genres: Formulas, Filmmaking, and the Studio System (New York: Random House, 1981), 38. 28 Schrader, "Notes", 59.

filmjournal.org filmjournal.sercia@gmail.com Although the cold war era was in many regards a period of a "return to normalcy" as far as traditional gender roles are concerned, it was considered in the contemporary media as a period of reversal of gender roles, precisely because men were afraid of losing their prerogatives as breadwinners and heads of family. These anxieties were fuelled by the media of the 1950s who were passing on the message that there was a crisis in masculinity, and by a number of conservative "socially-oriented psychologists" [START_REF] Herman | The Romance of American Psychology: Political Culture in the Age of Experts[END_REF] who blamed social changes for disrupting traditional family values -for example, the rise in divorce rate, the public debate over male sexuality, the sexual and financial autonomy gained by women, and "momism." [START_REF] Chapman | Cherchez la Femme: The Searchers, Vertigo, and Masculinity in Post-Kinsey America[END_REF] These anxieties form the ideological background of the period. They tie up with what K. A. Cuordileone calls "a political culture that […] put a new premium on hard masculine toughness and rendered anything less than that soft, timid, feminine and as such, a real or potential threat to the security of the nation." [START_REF] Cuordileone | Prologue", Manhood and American Political Culture in the Cold War[END_REF] Her argument about the "softening" of men is linked to fears of communism:

The accusation of softness was the primary weapon with which Joe McCarthy and his allies clubbed their political enemies, who were not so much Communist, but eastern establishment liberals and internationalists.

32

In this way, cultural fears of decline of masculinity, and surrender of the male self were translated into a politics of anticommunism. The ideological background of The Narrow Margin refers explicitly to two interrelated and concomitant political major events: the Kefauver Commission, and the HUAC (U. S. House of Representatives Un-American Activities Committee) hearings which investigated alleged disloyalty and subversive activities on the part of private citizens and organizations suspected of Communist affiliations. These events are both products of Cold War tensions and both reveal the so-called "climate of paranoia." Munby notes that "images and stories about a syndicate-controlled society overlapped with Cold War concerns about Communist conspiracy." [START_REF] Munby | Public Enemies, Public heroes: Screening the Gangster from Little Caesar to Touch of Evil[END_REF] It seems that the film uses the trope of the locomotive to express these anxieties about the HUAC hearings and the generalized atmosphere of suspicion triggered by the Kefauver commission. This appears explicitly when Sinclair refers to the HUAC hearings when she tries to clarify the situation: filmjournal.org filmjournal.sercia@gmail.com This passage illustrates the preoccupation of the times with "the fact that nothing (including the judicial system, politics, real estate, the union, and trade) is immune to graft and mob control". 34 Along the same line of thought, Brown's puzzlement and lack of grasp expressed in his question "I've been played for a sucker. Why?" echoes the words of an entire lineage of film noir antiheroes in "a spate of 1950s syndicate 'exposé' features made following Senator Estes Kefauver's televised investigation of organized crime in 1950-1951." 35 This expresses as much the general paranoia about institutional power as the fear of infiltration and corruption of the institutions. This tense and ambivalent climate is rendered through Brown's eventful journey. The train is the "hellish mechanism" 36 that has replaced the femme fatale of early films noirs. While the early films noirs were about doomed characters obsessed with and influenced by bewitching women, The Narrow Margin displaces the origin of manipulation from the femme fatale to the train. Instead of being controlled for the purposes of a femme fatale, the male protagonist of The Narrow Margin is controlled by the institution that hires him and suspects him of taking bribes.

The train thus gives metaphorical expression to the rampant idea that an overpowering force that went beyond individual will and understanding controlled people's destinies. Simultaneously, Brown's bouts of hyper masculinity are revealing of his struggle to exculpate himself as a possible traitor. By showing how tough he is, he might be trying to avoid accusations of softness, and thereby of communism.

Conclusion

As she delivers the line "To better tracks and steadier nerves," Sinclair voices the conventional idea of the lack of self-control of the male protagonist since she suggests that the train makes him nervous. But these words also introduce a new dimension by implying that the train undermines the representation of the male protagonist as a tough cop. The conjunction "and" that linguistically joins two elements of the same type puts on an equal footing "better tracks" and "steadier nerves", bringing together a mechanical manifestation and an emotion, hence, human beings and machines. This anthropomorphic implication introduces the idea that the train affects the behavior of the male protagonist. This line is also a manifestation of the metafictional intent that informs the film and prompts a selfconscious look at film noir conventions and codes, one of the main ones being problematic male identity.

The triple implication of the line "To better tracks and steadier nerves" synthesizes the complex connections between the train, the camera, the protagonists and the plot. The parallel between humans and machines points to reification and anthropomorphism. It also suggests the influence of machines on humans in a process of enhancement and constriction. Finally, it also contains a metafictional comment on the process of storytelling and filmmaking, all of which I have tried to show in this analysis of The Narrow Margin. 34 Munby, Public Enemies, 133. 35 Ibid. 36 The introduction of the train helps to renew the traditional ingredients of film noir, in keeping with the studio system which works on the principle of variation and repetition, recycling the most successful elements of films and introducing new elements to old plots. Following this principle, The Narrow Margin brings into play a machine rather than a femme fatale, and thus gives new impetus to the character of the ambivalent noir hero torn between righteousness and corruption, self-confident manliness and lack of virility.

The train proves to be a perfect locale to convey the instability of the noir hero who has lost his grounding, both in the literal and figurative senses. The dialectics of enhancement and constriction as shown to be produced by this machine questions an alleged ultra-powerful manliness of the hero and brings us back to the fragility of the human condition. The train works as an objective correlative for the uncertainties about normative masculinity. At the same time, the fear of internal subversion of the institutions and the fear of manipulation of individuals by the institutions, two somehow contradictory but concurrent fears, have been pinned down as the historical background, and the film like most films released during the Cold War period can be said to translate the anti-Communist hysteria of the times.

Fig. 1

 1 Fig. 1

10

  There are famous fight sequences in classical films noirs such as The Maltese Falcon (John Huston, 1941), Murder My Sweet (Edward Dmytryk, 1944), The Big Sleep (Howard Hawks, 1946), and Where the Sidewalk Ends (Otto Preminger, 1950). 11 Frank Krutnik, In a Lonely Street, Film Noir, Genre, Masculinity, (London: Routledge, 1991), 190. 12 Sigmund Freud, Civilization and its Discontent [1930] The Standard Edition of the Complete Psychological Works of Sigmund Freud, trans. James Strachey, (London: Vintage, 2001 [1964]), 91-92. 13 Seltzer, Bodies, 18. filmjournal.org filmjournal.sercia@gmail.com

Fig. 2

 2 Fig. 2 Joseph Kemp (David Clarke) and Walter Brown (Charles McGraw)

Fig. 3

 3 Fig. 3 Walter Brown (Charles McGraw) and Sam Jennings (Paul Maxey)

Fig. 4

 4 Fig. 4

Fig. 5

 5 Fig. 5 Densel (Peter Virgo) seen from the back by Brown (Charles McGraw)

Forbes:

  Bet you wonder that same thing I am: what she looks like. Brown: I don't have to wonder. I know. Forbes: Why that's wonderful Walter. Nobody's seen her, but you know what she looks like. What a gift.

Fig. 6

 6 Fig. 6 Brown (Charles McGraw) gets angry because Neal (Mary Windsor) suggests that the gangsters should choose Mrs. Sinclair as a target instead of her.

  "une mécanique infernale," Jean-Pierre Esquenazi, Le Film noir: Histoire et significations d'un genre populaire subversif (Paris: CNRS editions, 2012), 310. filmjournal.org filmjournal.sercia@gmail.com

Mark Seltzer, Bodies and Machines (New York and London: Routledge, 1992), 8.

Hirsch, Dark Side, 200.

See the introduction to this issue on "Railway and Locomotive Language in Film" by Taina Tukhunen, paragraph, 3.

Seltzer, Bodies, 19.

Hirsch, Dark Side, 86, 85.

Seltzer, Bodies, 4.

Ibid.

Ibid.

Wim Wenders, "Preface," in Travellings du rail, Daniel Corinaut and Roger Viry-Babel (Paris: Editions Denoël, 1989), 11.

Ibid. "le paysage passe comme sur un grand écran et on y est le seul témoin d'un travelling magnifique."

Martine Joly, L'image et les signes : approche sémiotique de l'image fixe (Paris : Nathan, 1994), 96-102.

Alain Masson, "Richard Fleischer-le vertige et l'élan," Positif, Revue mensuelle de cinéma, no. 544 (2006), 97 (my translation).

Chandler, "The Simple Art of Murder," 991.

COD: "Cash On Delivery."

Hirsch, Dark Side, 202.

Henri Bergson, Laughter: An Essay on the Meaning of the Comic, trans. Cloudesley Brereton and Fred Rothwell, (Mineola: Dover, 2005 [1911]), 24.


Zach Shahn
email: zachary.shahn@sph.cuny.edu

Aman Choudhri

Boris Jung

Daniel Talmor

Li-Wei H Lehman

Elias Baedorf-Kassis

Effects of aggressive and conservative strategies for mechanical ventilation liberation

Keywords:

Background:

The optimal approach for transitioning from strict lung protective ventilation to support modes of ventilation when patients determine their own respiratory rate and tidal volume remains unclear. While aggressive liberation from lung protective settings could expedite extubation and prevent harm from prolonged ventilation and sedation, conservative liberation could prevent lung injury from spontaneous breathing.

Research question:

Should physicians take a more aggressive or conservative approach to liberation?

Methods:

Retrospective cohort study of mechanically ventilated patients from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version 1.0) estimating effects of incremental interventions modifying the propensity for liberation to be more aggressive or conservative relative to usual care, with adjustment for confounding via inverse probability weighting. Outcomes included in-hospital mortality, ventilator free days, and ICU free days. Analysis was performed on the entire cohort as well as subgroups differentiated by PaO2/FiO2 ratio, and SOFA.

Results:

) with an aggressive strategy doubling liberation odds, and 74 h (0.95 CI = [69,78]) under a conservative strategy halving liberation odds). In the full cohort, we estimated aggressive liberation increased ICU-free days by 0.9 days (0.95 CI = [0.8,1.0]) and ventilator free days by 0.82 days (0.95 CI = [0.67,0.97]), but had minimal effect on mortality (only a 0.3% (0.95 CI = [ 0.2%,0.8%]) difference between minimum and maximum rates). With baseline SOFA≥ 12 (n = 1355), aggressive liberation moderately increased mortality (58.5% [0.95 CI = (55.7%, 61.2%)]) compared with conservative liberation (55.1% [0.95 CI = (51.6%,58.6%)]).

Interpretation:

. Distributions over all patient-hours in the cohort of estimated probabilities of liberation under three treatment regimes-usual care, "aggressive" (corresponding to an incremental intervention with δ = 2), and "conservative" (corresponding to an incremental intervention with δ = 12).

Introduction

Lung protective mechanical ventilation strategies have become the standard of care to prevent lung injury and improve morbidity and mortality in patients requiring mechanical ventilation [START_REF] Brochard | Mechanical ventilation to minimize progression of lung injury in acute respiratory failure[END_REF][START_REF] Grasso | ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure[END_REF][START_REF] Amato | Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome[END_REF]. While lung protective mechanical ventilation is of critical importance, the goal for all ventilated patients is successful extubation and removal of mechanical support. The final steps in weaning from the ventilator to determine readiness for extubation have been extensively investigated with data from multiple studies to guide clinical decision making [START_REF] Girard | Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (awakening and breathing controlled trial): a randomised controlled trial[END_REF][START_REF] Kress | Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation[END_REF][START_REF] Meade | Predicting success in weaning from mechanical ventilation[END_REF], however we know very little about the initial liberation toward extubation when patients transition from lung protective ventilation to a support mode of ventilation. After this transition from tightly controlled settings, patients determine their own respiratory rate and tidal volumes with the ventilator providing support with each breath to augment the inspiratory effort. It remains unclear when it is safe to liberate patients from the rigid parameters of protective ventilation, with potential risks and benefits of both maintenance of lung protection and liberation.

Lung protective ventilation strategies require the strict application of low tidal volumes and non-injurious pressures [START_REF] Nieman | Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury[END_REF][START_REF] Neto | Association between tidal volume size, duration of ventilation, and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis[END_REF], which may cause patient discomfort. Assuring tolerance of these settings often requires high levels of sedation and/or paralytics [START_REF] Vinayak | The relationship between sedative infusion requirements and permissive hypercapnia in critically ill, mechanically ventilated patients[END_REF] with the use of these potentially causing delayed weaning, prolonged duration of mechanical ventilation, increased critical illness myopathy, increased delirium, and worsened mortality [START_REF] Rawal | Post-intensive care syndrome: an overview[END_REF][START_REF] Wongtangman | Optimal sedation in patients who receive neuromuscular blocking agent infusions for treatment of acute respiratory distress syndrome-a retrospective cohort study from a New England Health Care Network[END_REF][START_REF] Chanques | Impact of ventilator adjustment and sedationanalgesia practices on severe asynchrony in patients ventilated in assist-control mode[END_REF][START_REF] Ely | Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS)[END_REF][14]. Furthermore, prolonged intubation may lead to complications such as ventilator associated pneumonias and the need for tracheostomy [START_REF] Rawal | Post-intensive care syndrome: an overview[END_REF]. To limit these harms it may be beneficial to expedite weaning from strict lung protective ventilation parameters to allow for lower sedation requirements. However, it is also possible that allowing patients to breathe spontaneously before they have adequately recovered from their critical illness may result in worsened injury or further impact patient hemodynamics [START_REF] Su | PPV may be a starting point to achieve circulatory protective mechanical ventilation[END_REF][START_REF] Cortes-Puentes | Physiology-guided management of hemodynamics in acute respiratory distress syndrome[END_REF][START_REF] Dreyfuss | High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure[END_REF]. While spontaneous breathing may be beneficial in less sick patients with improved ventilation/perfusion matching and more physiologic breathing [START_REF] Yoshida | The role of spontaneous effort during mechanical ventilation: Normal lung versus injured lung[END_REF], this may not be the case for sicker patients with potentially injurious pressure and volume subsequently leading to worsened lung injurywhat has been described as patient self-induced lung injury (P-SILI) [START_REF] Yoshida | Patient self-inflicted lung injury and positive end-expiratory pressure for safe spontaneous breathing[END_REF][START_REF] Tobin | P-SILI is not justification for intubation of COVID-19 patients[END_REF][START_REF] Yoshida | Spontaneous effort during mechanical ventilation: maximal injury with less positive end-expiratory pressure[END_REF][START_REF] Yoshida | Spontaneous breathing during mechanical ventilation-risks, mechanisms and management[END_REF][START_REF] Brochard | Ventilation-induced lung injury exists in spontaneously breathing patients with acute respiratory failure: yes[END_REF].

In this paper, we take an important first step toward assessing the tradeoffs involved in liberation timing. Using a recently developed technique, we estimate the effects of so-called incremental interventions [START_REF] Kennedy | Nonparametric causal effects based on incremental propensity score interventions[END_REF] that shift the probability (or, more precisely, multiply the odds) of liberation given patient history at each time relative to usual care. If a patient were very unlikely to be liberated at a given time under usual care due to their clinical characteristics (i.e. they remain severely ill or have a reason to not be weaned such as brain injury), incremental interventions (because they are multiplicative) would not markedly increase or decrease the absolute likelihood of liberation. If, on the other hand, there is considerable variation in whether a patient with a given history would be liberated under usual care, then incremental interventions would result in a much larger shift in absolute probability of liberation. In other words, incremental interventions mostly impact those patients in whom there is significant variation in care under usual care, a desirable property.

Note that incremental interventions are not directly actionable, as they do not specify exactly in which scenarios clinicians should liberate. While it would be ideal to identify actionable interventions that improve on usual care, we study incremental interventions because they sidestep analytic barriers to reliably estimating effects of actionable treatment rules in a complicated decision making setting. To be realistic, an actionable liberation strategy would need to be complex, basing decisions on a large number of variables including and not limited to ventilator settings, type and timing of lung injury, level of sedation, and sedative choice. In observational datasets, very few patients would follow any such complex strategy precisely, making it difficult to reliably estimate its effects. In contrast, simplified rules that might be followed by a larger number of patients would (due to their insufficient complexity) likely call for liberations in scenarios in which the probability of liberation under usual care is close to 0, which is called a "positivity violation" and can make estimation of causal effects highly unstable. Incremental interventions avoid these analytic challenges [START_REF] Kennedy | Nonparametric causal effects based on incremental propensity score interventions[END_REF], making them well suited for this study.

In addition to being tractable, incremental intervention effects can also be highly suggestive about how care should change and inform the design of future randomized trials whose results would be actionable. For example, if aggressive incremental interventions making liberation more likely than under usual care (given patient history) are estimated to be beneficial, this would imply that on average physicians would do better to look for earlier opportunities to liberate. But most importantly, such results would suggest a need for randomized trials testing actionable protocols for aggressive liberation. Fig. 3. Hourly probability of liberation under usual care, an aggressive incremental intervention (δ = 2), and a conservative incremental intervention (δ =12) for two representative patients-one with high hourly probability of liberation (Left), and one with low hourly probability of liberation (Right). Unsurprisingly, the patient with high probability of liberation was liberated sooner (after 5 h) than the patient with lower hourly probability of liberation (86 h). Each patient's estimated hourly probability of liberation under usual care fluctuates with time varying covariates, and the probabilities of liberation under incremental interventions fluctuate along with the usual care probabilities. In the patient with higher probabilities of liberation under usual care, the impact of the incremental interventions on probability of liberation on an absolute scale is much larger than in the patient with low probabilities of liberation.

Methods

Cohort construction

We performed a retrospective cohort study of mechanically ventilated patients from the Medical Information Mart for Intensive Care IV database (MIMIC-IV version 1.0), publicly available at PhysioNet. The database contains records from 64,975 hospital admissions between 2008 and 2019 to Beth Israel Deaconess Medical Center, a tertiary academic medical center in Boston, MA, USA. Institutional review boards at Beth Israel Deaconess Medical Center (BIDMC) (2001-P-001699/14) and Massachusetts Institute of Technology (0403000206) have approved use of MIMIC-IV for research and granted waiver of informed consent.

Inclusion criteria were that patients needed to be mechanically ventilated in a control mode for 24 consecutive hours after ICU admission without a liberation attempt. Liberation attempts were defined as switches from controlled modes of ventilation to support modes of ventilation. We excluded patients with records of previous ICU admission at BIDMC. Patients were entered into the cohort at the first time that inclusion criteria were met (Fig. 1). Control modes are listed in the supplementary materials.

For each patient in our cohort, we extracted baseline variables including: age, sex, weight, first care unit, admission type, select Elixhauser comorbidities, and a baseline frailty score. We also extracted time-stamped, time-varying variables over the course of follow-up, including: vital signs (heart rate, respiratory rate, arterial pressure, temperature, spO2), lab values (PH, PO2, PCO2, AADO2), fluid volume, vasopressor dose, sedation level, SOFA score, and both set and observed ventilator readings (PEEP, standardized tidal volume, peak inspiratory pressure, mean airway pressure, PaO2-FiO2 ratio, inspiratory time, driving pressure, compliance). Our constructed dataset contained a row for each post-baseline patienthour when there had not been a prior liberation attempt. At each patient-hour, we input the most recent measurement of each covariate listed above and included an indicator for whether an initial liberation attempt occurred in that patient-hour. Missingness was rare (<5% of person times were missing for every covariate we adjusted for), and we imputed missing values with cohort medians.

Outcomes

We considered in-hospital mortality as the primary endpoint for the analysis. Additional secondary endpoints included ICU-free days, and ventilator-free days as outcomes. ICU free days were defined as the number of the 30 days following baseline (i.e. after 24 consecutive hours ventilated in control mode) that a patient was alive and not in an ICU at BIDMC. If a patient died out of hospital or was admitted to an ICU at another hospital during this time, this was not captured in our data. Ventilator-free days were defined analogously as the number of the 30 days following baseline that a patients was alive and not invasively ventilated. Additional subgroup analysis was also performed in patients with SOFA ≥ 12, SOFA ≤5, PaO2-FiO2 ratio ≤ 150, and PaO2-FiO2 ratio ≥ 300 at baseline. The subgroup analyses simply entailed conducting the analyses described below in these subgroups.

Effects of interest: incremental interventions

We estimated effects of incremental interventions adjusting for time-varying confounding via inverse probability weighting [START_REF] Kennedy | Nonparametric causal effects based on incremental propensity score interventions[END_REF]. An incremental intervention multiplies the odds of liberation given patient history at a given time under usual care by a factor δ. Values of δ <1 correspond to conservative interventions that prolong the average time until the first liberation attempt, and values of δ >1 correspond to aggressive interventions that shorten the average time to first liberation attempt. For example, suppose that under usual care 1 out of every 10 patients who had a particular history of recorded covariates (vital signs, ventilator settings, etc.) would be liberated at a given hour under usual care. (So the odds of liberation for patients with this history at this hour under usual care are 1 to 9.) Under an aggressive incremental intervention (δ = 2) doubling odds of liberation at each hour relative to usual care, the odds of liberation for patients with this history would become 2 to 9, meaning that 2 out of every 11 patients with this history would be liberated. Because incremental interventions are based on propensity to liberate under usual care, they do not call for unrealistic liberation attempts or delays that would never occur in practice. If a patient is very unlikely to be liberated at a given time under usual care, under the 'aggressive' intervention corresponding to δ = 2 their odds of liberating at that time would be doubled, but they would still be unlikely to be liberated on an absolute scale. Thus, most of the impact of an incremental intervention is in patients in whom there would be variation in care under usual care, a desirable property. Figs. 2 and 3 illustrate the impact of incremental interventions on hourly propensity to liberate relative to usual care. Fig. 2 shows the impact of these interventions on the distribution of hourly propensity to liberate in the cohort, and Fig. 3 illustrates their impact using data from two specific patients.

To formalize, at a given time t, let ht denote a patient's covariate and treatment history through t. Let πt(ht) denote the probability under usual care of an initial liberation attempt at time t conditional on history ht and no previous liberation attempts prior to t. We estimated expected population outcomes under interventions that multiply the conditional odds of an initial liberation attempt at each hour relative to usual care by a factor of δ, for δ in a range of values between 0.5 and 2.

Statistical analysis

For outcome Y, we estimate the expected value of Y under an intervention multiplying conditional liberation odds at each hour by δ (denoted E[Y(δ)] in counterfactual notation) adjusting for time-varying confounding via inverse probability weighting as

In the above formula, n is the sample size, patients are indexed by i and time (in hours) by t, and Ait indicates whether liberation occurred at hour t in patient i. π(hit) is the estimated conditional probability of liberation in patient i at time t under usual care, which we obtain from a pooled logistic regression model using the most recent value of each covariate listed in the cohort construction section as predictors. We provide a summary of this probability of liberation model including all covariates in the supplementary materials. If our probability of liberation model is well specified and the covariates we included in that model contain the drivers of liberation decisions that are also associated with outcomes of interest (or appropriate rich proxies), then our estimates of incremental effects are approximately unbiased. We estimated confidence intervals via bootstrap. R code for the analysis is available at https://github.com/zshahn/when_to_liberate .

Results

7433 patients met inclusion criteria and were included in the cohort for analysis. On average, patients in the cohort were liberated for the first time 43 h after baseline. The observed inhospital mortality rate in the overall cohort was 34%. On average, patients had 14 ICU-free days and 17 ventilator free days out of the 30 days following baseline. Baseline characteristics of the cohort are described in detail in Table 1.

Incremental interventions multiplying the odds of a first liberation at each hour relative to usual care were estimated to have a large impact on the average time after baseline to first liberation attempt (Fig. 4). Under usual care (i.e. δ = 1), the average time from baseline to first liberation attempt was about 43 h. Doubling the odds of liberation at each hour (i. e. δ = 2), was estimated to decrease the average time to first liberation attempt to about 24 h (0.95 CI = [START_REF] Brochard | Ventilation-induced lung injury exists in spontaneously breathing patients with acute respiratory failure: yes[END_REF][START_REF] Mauri | Spontaneous breathing: a double-edged sword to handle with care[END_REF]) after baseline. Halving the odds of liberation at each hour (i.e. δ = 0.5), was estimated to increase the average time to first liberation attempt to about 74 h (0.95 CI = [69,78]). Despite their large impact on average time to liberation, incremental interventions making liberation more or less likely were estimated to have very little effect on the full cohort in-hospital mortality rate (Fig. 5). The difference between the minimum and maximum full cohort mortality rates under the range of interventions considered was 0.3% (0.95 CI = [ 0.2%,0.8%]). Similar results held in the low baseline PaO2-FiO2 ratio (≤150) subgroup (n = 1837), the high baseline PaO2-FiO2 ratio (≥ 150) subgroup (n = 2024), and the low SOFA (≤5) subgroup (n = 2571). However, incremental liberation interventions were estimated to have a moderate effect in the subgroup of patients with baseline SOFA ≥ 12 (n = 1355). The in-hospital mortality rate in this group was 57.4%. The estimated mortality rate under a strategy aggressive relative to usual care in the subgroup (i.e. δ = 2) was 58.5% (0.95 CI = [55.7%,61.2%]). The estimated mortality rate under a strategy conservative relative to usual care in the subgroup (i.e. δ = 0.5) was 55.1% (0.95 CI = [51.6%,58.6%]. While incremental interventions did not rise to the level of impacting mortality in the full cohort, they were estimated to affect ICU-free days (Fig. 6) and ventilator free days (Fig. 7). An aggressive liberation strategy (i.e. δ = 2) was estimated to increase ICU-free days by 0.9 days (0.95 CI = [0.8,1.0]) and increase ventilator free days by 0.82 days (0.95 CI = [0.67,0.97]) relative to usual care in the full cohort. A conservative liberation strategy (i.e. δ = 0.5) was estimated to decrease ICU-free days by 1.5 days (0.95 CI = [1.3,1.7]) and ventilator free days by 1.55 days (0.95 CI = [1.31,1.79]) relative to usual care in the full cohort. Similar results were obtained for the PaO2-Fio2 ratio subgroups and the low baseline SOFA subgroup. But incremental interventions were estimated to have much smaller effects on ICU and ventilator free days in the high baseline SOFA subgroup. In this subgroup, usual care was estimated to be very close to optimal (across the range of incremental interventions).

Discussion

Interpretation of results

There is a great deal of uncertainty surrounding liberation timing from control mode ventilation to spontaneous modes of ventilation in mechanically ventilated patients without data to guide decision making. With aggressive strategies, early liberation attempts could have the potential to lead to early weaning, which could have the beneficial effects of reducing the level of required sedation and the total duration of time ventilated, limiting the potential harm associated with these. Alternatively, liberating too early and allowing spontaneous breathing could lead to self-inflicted lung injury [START_REF] Yoshida | Patient self-inflicted lung injury and positive end-expiratory pressure for safe spontaneous breathing[END_REF][START_REF] Mauri | Spontaneous breathing: a double-edged sword to handle with care[END_REF][START_REF] Yoshida | Spontaneous breathing during lung-protective ventilation in an experimental acute lung injury model: high transpulmonary pressure associated with strong spontaneous breathing effort may worsen lung injury[END_REF][START_REF] Telias | Acceptable range of inspiratory effort during mechanical ventilation: the effort study[END_REF], which could theoretically prolong mechanical ventilation time and increase the burden of sedation leading to other adverse outcomes [START_REF] Wongtangman | Optimal sedation in patients who receive neuromuscular blocking agent infusions for treatment of acute respiratory distress syndrome-a retrospective cohort study from a New England Health Care Network[END_REF]. In this study, we estimated that on average interventions shifting liberation strategies to be more aggressive relative to usual care would increase ICU and ventilator free days to a clinically meaningful and statistically significant degree while having very little impact on inhospital mortality. (However, in the subgroup of patients with high baseline SOFA score (≥ 12), more conservative liberation strategies were estimated to moderately decrease mortality, while incremental interventions on liberation timing were estimated to have very little effect on ICU and ventilator free days.) The implication of our results for patient care (assuming the results are not due to confounding) is that on average physicians could look for earlier opportunities to liberate patients who do not have very high baseline SOFA scores or have other reasons to not pursue liberation due to their clinical state. More importantly, the results suggest a need for randomized trials testing actionable protocols for aggressive liberation strategies more conclusively, as they could have the potential to meaningfully impact clinical outcomes.

Although the precise reasons for the estimated beneficial effects of aggressive liberation strategies on ICU and ventilator free days need further exploration, it is plausible that harmful effects from prolonged sedation under more conservative strategies are on-average worse or more common than harm from lung injury or hemodynamic compromise resulting from spontaneous breathing. Trialing spontaneous breathing may have little negative impact in the majority of patients even if they are unable to continue weaning further, so long as they are not left on injurious settings for a prolonged duration. That beneficial effects of aggressive liberation strategies were observed to a much lesser extent in the high baseline SOFA subgroup might be explained by the fact that many of these patients have a fairly low ceiling on ICU and ventilator free days due to the severity of their condition.

Interpretation of incremental interventions

As we have previously stressed, incremental interventions are not directly actionable in that they do not specify exactly under which circumstances to attempt liberation. Rather, incremental interventions are stochastic and preserve the uncertainty that exists under usual care about who will be liberated when. Because incremental interventions are defined multiplicatively relative to usual care, they do not call for unrealistic interventions in situations where liberation is very unlikely under usual care for good reason. Of course, ideally we could identify optimal actionable treatment rules for liberation, or at least actionable treatment rules that improve on usual care. We only consider incremental interventions instead because they sidestep analytic challenges in estimating effects of complex treatment rules from observational data while remaining informative. Beneficial effects of incremental interventions that are aggressive relative to usual care do not inform clinicians which patients they might be waiting too long to liberate, but do suggest that clinicians look even harder for opportunities to liberate than they previously had been. Again, the most important interpretation of a beneficial effect of an aggressive incremental intervention is the need for randomized trials testing specific actionable aggressive liberation strategies.

Limitations

A limitation of our analysis is that the treatments we considered intervened only on the odds of liberation conditional on patient state, including sedation level. As such, our results do not offer guidance on when to begin reducing sedation in preparation to liberate. Really, a joint sedation and liberation strategy is desired, and this analysis is just a step in that direction.

Another potential limitation of this analysis, as with any observational study attempting to estimate causal effects, is the potential presence of unobserved confounders. We believe that the set of baseline and time-varying confounders we adjusted for contained most relevant information about patient state that might influence liberation decisions and be associated with outcomes of interest. Further, we would expect similar unobserved confounders to bias estimates of effects on mortality and on ICU and ventilator free days, with healthier patients being liberated earlier and having better outcomes. It is therefore reassuring regarding the potential for unobserved confounding that we did not estimate any effect on mortality in the full cohort and a beneficial effect from conservative strategies in the high-risk subgroup. Still, we reiterate that we hope randomized trials might be conducted to more conclusively explore the effects of aggressive liberation strategies.

Fig. 4 .

 4 Fig. 4. Estimated average hours to first liberation attempt (and bootstrap confidence intervals) under a range of incremental interventions making liberation strategies more or less aggressive relative to usual care for the full cohort and subgroups defined in terms of baseline SOFA score and baseline PaO2-FiO2 ratio. The vertical lines at δ = 1 indicate usual care. To the left of these lines are more conservative liberation strategies and to the right are more aggressive liberation strategies. The figure shows that incremental interventions do indeed have a large impact on the treatment of interest.

Fig. 5 .

 5 Fig. 5. Estimated in-hospital mortality rates (and bootstrap confidence intervals) under a range of incremental interventions making liberation strategies more or less aggressive relative to usual care for the full cohort and subgroups defined in terms of baseline SOFA score and PaO2-FiO2 ratio. The vertical lines at δ = 1 indicate usual care. To the left of these lines are more conservative liberation strategies and to the right are more aggressive liberation strategies. Changing the aggressiveness of liberation strategies is estimated to have very little effect on mortality rate in the full cohort and PaO2-FiO2 ratio subgroups. More conservative strategies are estimated to lead to slightly lower mortality rates in the high SOFA subgroup.

Fig. 6 .

 6 Fig. 6. Estimated average ICU free days (and bootstrap confidence intervals) under a range of incremental interventions making liberation strategies more or less aggressive relative to usual care for the full cohort and subgroups defined in terms of baseline SOFA score and baseline PaO2-FiO2 ratio. The vertical lines at δ = 1 indicate usual care. To the left of the line are more conservative liberation strategies and to the right are more aggressive liberation strategies. More aggressive liberation strategies are estimated to increase ICU-free days in the general cohort. In the high SOFA subgroup, usual care is close to optimal in the class of strategies considered.

Fig. 7 .

 7 Fig. 7. Estimated average ventilator free days (and bootstrap confidence intervals) under a range of incremental interventions making liberation strategies more or less aggressive relative to usual care for the full cohort and subgroups defined in terms of baseline SOFA score and baseline PaO2-FiO2 ratio. The vertical lines at δ = 1 indicate usual care. To the left of the lines are more conservative liberation strategies and to the right are more aggressive liberation strategies. More aggressive liberation strategies are estimated to increase ventilator free days in the general cohort. In the high SOFA subgroup, usual care is close to optimal in the class of strategies considered.

Acknowledgements

Authors Contributions: ZS, LL, AC, DT and EBK conceptualized the study. AC, ZS, and LL extracted data and/or performed analysis on the data. ZS and EBK primarily wrote manuscript with critical review and editing by all authors. ZS serves as the guarantor of the paper.

Authors contributions

ZS, LL, AC, DT and EBK conceptualized the study. AC, ZS, and LL extracted data and/or performed analysis on the data. ZS and EBK primarily wrote manuscript with critical review and editing by all authors. ZS serves as the guarantor of the paper.

Declaration of Competing Interest

This work was conducted by EBK with the support of a KL2 award (an appointed KL2 award) from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR002542). Funding was also provided by the MIT-IBM Watson AI Lab and NIH grant 5R01 EB017205. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. EBK and DT having received lecturing fees for educational talks from Hamilton Medical Inc. ZS was primarily employed by IBM Research during much of the work.