COMFORT AND DISTRESS IN THE ICU: SCOPE OF THE PROBLEM

The management of sedation, analgesia, and neuromuscular blockade (NMB) is extensively woven into the fabric of contemporary care of critically ill patients. A decade ago, Hansen-Flaschen and colleagues[1] documented the near-universal usage of sedating and paralytic medications in U.S. intensive care units (ICU). Over one third of surveyed ICUs reported using sedating drugs in at least 70% of their mechanically ventilated patients. The authors noted a wide variability in utilization patterns and called for research to determine optimal use. Recent national surveys of Danish[2] and Australian[3] ICUs confirm the common practice of administering sedative medications to mechanically ventilated ICU patients. In a prospective study, 62 critical care pharmacists documented administration of sedative, analgesic, and paralytic drugs on 62% of patient-days during a 5-day period.[4] Dasta and coworkers[5] prospectively documented use of drugs for sedation, anxiety, pain, or neuromuscular blockade in 91% of consecutive adult surgical ICU patients. In a recent analysis of 200 adult ICU patients at our institution, 57% of patients receiving mechanical ventilation and 42% of patients breathing without support had been given sedative or narcotic analgesic medications in the previous 24 hours. Continuous infusion delivery was utilized in 26% of treated patients, most of whom were receiving mechanical ventilation. Sedative and analgesic drugs were used in the majority of patients in the medical, surgical, and cardiac surgical ICUs, and less frequently in the neuroscience and coronary ICUs.

Common indications for analgesic and sedative drugs are to minimize anxiety, to relieve pain and discomfort, to improve patient tolerance of mechanical ventilation and thereby optimize patient-ventilator synchrony, and to control agitated behavior and distress. Additional indications include enhancing amnesia, promoting sleep, reducing oxygen consumption, and preventing myocardial ischemia. The commonly cited indication of enhanced patient tolerance of mechanical ventilation arises in part from ongoing advances in mechanical ventilator technology as well as our understanding of pathophysiology of conditions such as the acute respiratory distress syndrome (ARDS) and status asthmaticus. We increasingly use unconventional, and often uncomfortable, forms of mechanical ventilation such as small tidal volume ventilation, permissive hypercapnia, inverse ratio ventilation, and pressure control ventilation.[6] [7] [8] The development of intrinsic or auto positive end-expiratory pressure (PEEP), among the most insidious and potentially dangerous complications of mechanical ventilation, can be dramatically worsened by inadequately controlled anxiety or pain.

Prevention of self-induced injury or injury to caregivers is another high priority for effective sedation. Unplanned extubation or self-removal of other critical tubes or vascular catheters is a common, and potentially immediately life-threatening, action. Approximately 9% of ICU endotracheal (ET) tube extubations are unplanned, the vast majority being self-extubation rather than accidental dislodgment.[9] Recently Carrion et al[10] documented self-removal rates of 24.7, 73.9, 12.4, and 46.5 per 1000 days for ET tubes, nasoenteric (NE) tubes, central venous catheters, and arterial catheters, respectively. In a prospective study of 128 medical ICU patients, 35 (ET) tubes, NE tubes, and vascular catheters were removed by agitated patients for a total rate of 132 tube or catheter removals per 1000 patient-days.[11] Further, events characterized by aggressive behavior toward nurses and other caregivers occurred at a rate of 91 per 1000 patient-days.[11] Additional important adverse consequences of inadequate analgesia and sedation range from myocardial ischemia resulting from an exaggerated stress response characterized by increased sympathetic nervous system activity, to diminished immune function and impaired wound healing associated with persistent pain.[12] [13]

For such simple therapeutic end-points of patient comfort and safety, the issues that influence management are numerous and often dynamic over time. Achieving this delicate balance of patient comfort without having excessive or prolonged reduction in level of consciousness, persistent muscular weakness, or other complications is a complex task. Factors that influence the patient's level of comfort and need for pharmacological intervention for anxiety, pain, delirium, and discomfort are numerous and include preexisting medical conditions, acute medical or surgical illness(s), concurrent events such as iatrogenic illness and invasive procedures, other medications, sleep deprivation, and environmental factors. Further, the salutary as well as adverse effects of sedative and paralytic medications are often influenced by drug-drug interactions and organ dysfunction, which influence drug metabolism as well as the likelihood of adverse effects of medications.

The cost of patient comfort can be considerable in terms of patient well-being as well as resources consumed. Adverse effects of sedative, analgesic, neuroleptic, and paralytic medications are well described. Some adverse effects can be anticipated while others, such as neuromuscular blocking agent (NMBA)-related myopathy, are less predictable, but potentially devastating.[14] [15] The untoward effects of sedating medications can be insidious, resulting in unrecognized delays in extubation and ICU discharge. Recent prospective trials provide convincing evidence that conventional use of continuous sedative and analgesic medication infusion can be linked to prolonged duration of mechanical ventilation, longer ICU and hospital length of stays, and increased frequency of tracheostomy.[16] [17] There are important financial costs associated with these additional days of care. Furthermore, sedative medications are said to account for 10 to 15% of pharmacy costs for ICU patients.[18] When average daily doses of sedatives administered in prospective clinical trials are multiplied by current acquisition costs, it is apparent that these daily costs can exceed U.S.$500.00 for a single medication.[19] [20]

As in many aspects of pharmacological therapy, successful management of anxiety, delirium, and pain requires logical strategies to use the proper dosage of the most appropriate medication(s) to achieve stated end-points based on individual patients' needs and clinical characteristics. Tools such as sedation scales[21] [22] [23] and delirium rating scales[24] [25] aid in recognition and description of important conditions and promote more precise drug titration, yet they remain underutilized.[26] Guidelines for sedation and analgesia are increasingly used in ICUs. Recently, prospective randomized trials of guidelines that focus on targeted dosage reductions have demonstrated reduced lengths of stay, less diagnostic testing, and fewer tracheostomies, without documented ill effect such as unplanned extubation.[16] [17] The effects of these aggressive dose-reducing strategies on patient comfort and neuropsychological function are yet to be established. The use of guidelines reduces variation in practice, but the particular needs of the individual patient must also be considered to achieve optimal management. Important factors include recognition and treatment of pain and delirium, titration of medications to the specific level of sedation needed for that patient at that particular time (i.e., the patient who requires uncomfortable forms of mechanical ventilation for ARDS may need deeper sedation than the patient who is improving and weaning from ventilatory support), and consideration of organ dysfunction in drug selection and dosing. The numerous factors that influence the future management of these common and complex issues of sedation, analgesia, and neuromuscular blockade are address in the subsequent articles of this issue of Seminars.

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