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Chapter 1 Introduction CHAPTER 1 INTRODUCTION And what of the god of sleep, patron of anaesthesia? The centuries themselves number more than 21 since Hypnos wrapped his cloak of sleep over Hellas. Now before Hypnos, the artisan, is set the respiring flame – that he may, by knowing the process, better the art. John W. Severinghaus When, in 1969, John Severinghaus penned that conclusion to his foreword for the first edition of John Nunn’s Applied Respiratory Physiology (Nunn 1969), he probably did not have in mind a potential interaction between surgery, anaesthesia, analgesia and postoperative sleep. It is only since then that we have identified the importance of sleep after surgery and embarked upon research into this aspect of perioperative medicine. Johns and his colleagues (Johns 1974) first suggested and examined the potential role of sleep disruption in the generation of morbidity after major surgery in 1974. It soon became clear that sleep-related upper airway obstruction could even result in death after upper airway surgery (Kravath 1980). By the mid-eighties, sleep had been implicated as a causative factor for profound episodic hypoxaemia in the early postoperative period (Catley 1985). The end of that decade saw the first evidence for a rebound in rapid eye movement (REM) sleep that might be contributing to an increase in episodic sleep- related hypoxaemic events occurring later in the first postoperative week (Knill 1987; Knill 1990). Since then, speculation regarding the role of REM sleep rebound in the generation of late postoperative morbidity and mortality (Rosenberg-Adamsen 1996a) has evolved 1 into dogma (Benumof 2001) without any direct evidence to support this assumption. Controversy has also arisen regarding the role of sleep in the causation of early postoperative respiratory disturbances (Rahman 2001; Wu 2003). Thirty years of research, speculation and comment on the role of sleep and sleep- disordered breathing in the causation of perioperative morbidity have come and gone. In that time almost nothing has been said about the potential for anaesthetists, with the observations they make each day, to make an important contribution to the diagnosis and management of sleep-disordered breathing with its consequent morbidity. The imbalance needs to be redressed. The research presented in this Thesis was conducted to examine the importance of sleep in postoperative respiratory dysfunction, and to show that the daily observations made by anaesthetists in their management of the airway might be utilised to assist patients with sleep-disordered breathing in the longer term. The former involved two main areas: a search for evidence of a clinically important contribution of REM sleep rebound to postoperative morbidity and a re-examination of the role of sleep in the postoperative causation of episodic hypoxaemic events in general. To assess the latter, a relationship between airway obstruction under anaesthesia and the severity of sleep-disordered breathing was sought. How ironic it is that Hypnos, the patron of anaesthesia, should also be god of that sleep which could be snuffing out the respiring flame of those same patients. Let us further examine this irony and see if, by knowing the process and bettering the art as Severinghaus exhorted, we may once again bring harmony to the dual roles of Hypnos and keep alight the flame Severinghaus set before him. 2 CHAPTER 2 REVIEW OF THE LITERATURE Falstaff: Now, Hal, what time of day is it, lad? Prince Henry: Thou art so fat-witted, with drinking of old sack, and unbuttoning thee after supper, and sleeping upon benches after noon… Act I, Scene II Poins: Falstaff! - fast asleep behind the arras, and snorting like a horse. Prince Henry: Hark, how hard he fetches breath… Act II, Scene IV King Henry IV Part I William Shakespeare Although hypoxaemia in the postoperative period has been recognised for many years (Nunn 1962; Bay 1968; Papper 1971; Spence 1972; Jones 1990), the first examination of ventilatory patterns and their association with sleep in this period was carried out by Catley and his colleagues (Catley 1985). Studying only the first postoperative night, they found that all profound episodic oxygen desaturations in the postoperative period were caused by upper airway obstruction, occurring only during sleep. The effect of sleep on postoperative respiration has been a subject of interest since then. The finding by Knill’s group (Knill 1987) of a rapid eye movement (REM) sleep rebound, after an initial period of postoperative REM suppression, led them and others to speculate on the 3 potential consequences of a REM-related increase in hypoxaemic events in the late postoperative period. Despite a lack of direct evidence, much has since been made of the possible effect of this REM rebound on late postoperative morbidity and mortality. This review will examine the literature concerning sleep-related respiratory disorders, obstructive sleep apnoea in particular, and investigate what is already known or suspected about the effects of surgery and anaesthesia on sleep and postoperative sleep- related respiratory dysfunction. SLEEP-RELATED BREATHING DISORDERS While the first detailed description of obstructive sleep apnoea (OSA) only appeared in 1966 (Gastaut 1966), many had noted its characteristics prior to this. The best known of these descriptions is Dickens' portrayal of Joe the Fat Boy in The Posthumous Papers of the Pickwick Club, although it would seem that Shakespeare had observed the symptoms at least three centuries earlier. Considering Shakespeare's comic intent, it is clear that the audience would have been aware of them also. This suggests the problem to be a common one as several large studies now confirm (Stradling 1991; Young 1993c; Bearpark 1995; Young 2002). These studies demonstrate that between two and four percent of middle aged adults have clinically significant sleep apnoea with a male:female ratio of 2:1. It has been recently suggested (Sauret Valet 1999) that the symptoms of sleep apnoea had been observed and described nearly two millennia before Gastaut by Pliny the Younger (Gaius Plinius) in his account of the death of his uncle, Pliny the Elder, during the eruption of Vesuvius. A close examination of Pliny’s letter to the historian Tacitus in which he recorded the event, however, indicates Sauret Valet’s suggestion is rather imaginative. In the letter he described the actions of his uncle in Stabiae thus: “To alleviate people's fears my uncle claimed that the flames came from the deserted homes of farmers who had left in a panic with the hearth fires still alight. Then he rested, and gave every indication of actually sleeping; people who passed by his door heard his snores, which were rather resonant since he was a heavy man.” Later in the letter he 4 reports his uncle’s death: “Supported by two small slaves he stood up, and immediately collapsed. As I understand it, his breathing was obstructed by the dust-laden air, and his innards, which were never strong and often blocked or upset, simply shut down. When daylight came again two days after he died…” There is, therefore, little in Gaius Plinius’ letter apart from a description of heavy snoring to suggest his uncle had sleep apnoea. Definitions Until recently there has been no broad consensus regarding standard definitions, including thresholds of significance, for many of the terms used to describe sleep- related breathing disturbances. A recent report has addressed these issues (AASM 1999). It is generally but arbitrarily agreed that an apnoea, defined as a cessation of airflow, has to exceed ten seconds duration to be considered significant. Standard definitions for hypopnoea have been even more controversial (Meoli 2001). It is usually defined as a reduction in airflow or respiratory effort for more than ten seconds accompanied by a desaturation of three percent or more and/or electroencephalographic evidence of arousal (AASM 1999; Tsai 1999; Meoli 2001). The apnoea hypopnoea index (AHI) is the number of apnoeas and hypopnoeas per hour of sleep and is used more or less interchangeably with the term respiratory disturbance index (RDI) the term that will be used for the remainder of this thesis. The apnoeas may be obstructive, central or mixed. Obstructive apnoeas are characterised by persistent effort without airflow, while with central apnoea effort is absent. OSA, where the apnoeas are predominantly obstructive or mixed, is much more common than central sleep apnoea (CSA). Sleep disordered breathing (SDB) is a term commonly used to encompass both these and other related conditions, some of which are mentioned below. The term obstructive sleep apnoea syndrome (OSAS) is applied when OSA is accompanied by daytime sequelae such as excessive daytime sleepiness. As there is a continuum of possible RDIs from trivial to severe, defining the presence of clinically significant sleep apnoea is somewhat arbitrary. It is generally agreed that the RDI should exceed five to be considered significant, with some advocating an RDI of 5 ten or more. It has been suggested that an RDI of 5 to 15 represents mild sleep apnoea, 15 to 30 moderate and greater than 30 severe (AASM 1999). However, the magnitude of associated symptoms and hypoxaemia also need to be considered when severity is determined (Lugaresi 1983). These definitions of severity have never been considered from the point of view of their relevance to surgery and anaesthesia. Hoffstein and Szalai (Hoffstein 1993) found that even with the inclusion of a "clinical impression" by the examining sleep physician, clinical features could not reliably predict the presence or otherwise of OSA. Many patients, brought along to clinics by concerned bed partners who have witnessed apnoeas, deny symptoms. Conversely, some patients exhibiting all the daytime features of OSA have few apnoeas or hypopnoeas. Some of these habitual snorers have been found to have recurrent arousals from sleep resulting from increases in upper airway resistance not sufficient to cause apnoeas or hypopnoeas as usually defined, a condition sometimes referred to as upper airway resistance syndrome (Guilleminault 1993).
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