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Medications for analgesia and sedation in the intensive care unit: an overview
Diederik Gommers, Jan Bakker
Critical Care , 2008, DOI: 10.1186/cc6150
Abstract: Critically ill patients are often uncomfortable because of pain, anxiety, and reluctance to undergo mechanical ventilation. This discomfort is treated with continuous sedation, usually in combination with an opioid at low dose. However, continuous sedation has been associated with prolonged mechanical ventilation and a longer stay in the intensive care unit (ICU), whereas daily interruption of sedative treatment has been shown to reduce the duration of mechanical ventilation and ICU stay [1]. Therefore, a shift from deep to light sedation is currently recommended. In addition, recent studies suggest that analgesia-based sedation protocols are as effective as conventional hypnotic-based sedation protocols but that the required dose of hypnotic drug is reduced [2,3].Thus, meeting the goals of analgesia and sedation in the ICU may require a change in both protocols and drugs used. In this review we discuss the most commonly used drugs in the ICU, focusing on the short-acting agents.Analgesia should be titrated to the needs of the individual patient. This individual treatment plan usually consists of a basal regimen that is adapted to the patient's pain perception and general features (age, body mass, and so on), in combination with a rescue dose for incidental and procedural pain. Analgesics can be administered by enteral, transcutaneous and parenteral routes. However, delayed gastric emptying, (continuous) gastric drainage, decreased gut function, uncertain first-pass effect, general edema, and use of vasopressors, usually make the parenteral route preferable in critically ill patients. Parenteral drugs can be given by continuous infusion, bolus and patient-controlled analgesic techniques. In addition, epidural infusions of local anesthetics, often combined with opioids, can provide effective analgesia, for example in the case of fractured ribs or thoracic or abdominal wounds.Epidural analgesia is used extensively in modern anesthetic practice. A meta-analysis of more
Evaluating and monitoring analgesia and sedation in the intensive care unit
Curtis N Sessler, Mary Jo Grap, Michael AE Ramsay
Critical Care , 2008, DOI: 10.1186/cc6148
Abstract: Effective management of analgesia and sedation in the intensive care unit (ICU) setting requires an assessment of the needs of the patient, subjective and/or objective measurement of the key variables (such as pain, agitation, and level of consciousness), and titration of therapy to achieve specific targets [1-4]. It is important to recognize that patient needs can differ depending upon clinical circumstances, and that for any given patient therapeutic targets are likely to change over time. Thus, achieving patient comfort and ensuring patient safety, including avoidance of excessive or prolonged sedation, relies on accurately measuring pain, agitation, sedation, and other related variables utilizing validated tools that are easy to use, precise, accurate, and sufficiently robust to include a wide range of behaviors. The consequences of inadequate control of pain or agitation are considerable, but excessive or prolonged sedation is also problematic, leading to increased risk for complications of critical care. In addition to promoting a consistent, goal-directed approach to management, the systematic use of these tools enhances communication among care providers.Here we review the available subjective instruments for evaluating pain, sedation, and agitation in the critically ill adult patient, as well as the results of validation and clinical application studies. Additionally, although objective tools, such as cerebral function monitoring, have not achieved widespread application in the ICU setting, the principles and potential roles of objective measurements related to analgesia and sedation are discussed.Optimal pain assessment in adult critical care settings is essential because it has been reported that 35% to 55% of nurses underrate the patient's pain [5-7], and in one study [8] 64% of patients did not receive any medications before or during painful procedures. In the SUPPORT (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment) s
Analgesia and sedation in the intensive care unit: an overview of the issues
Curtis N Sessler, Wolfram Wilhelm
Critical Care , 2008, DOI: 10.1186/cc6147
Abstract: All clinicians who provide care to critically ill patients face many daily management challenges, including ensuring patient comfort and tolerance of the intensive care unit (ICU) environment, while avoiding complications related to therapy. This seemingly straightforward task of safely maintaining patient comfort in fact requires an appreciation of the many factors that may influence the patient's state of comfort or distress and the inter-relationship with ICU-related processes.Pain is the root cause of distress experienced by many ICU patients [1-4], but anxiety, dyspnea, delirium, sleep deprivation, and other factors can contribute and are often additive or synergistic [5-8]. The predisposing and causative conditions that provoke these components of distress range widely, and include underlying medical conditions (such as arthritis or chronic pain syndrome) and acute medical or surgical illness, as well as many 'routine' aspects of critical care such as mechanical ventilation, indwelling tubes and catheters, iatrogenic illness, medication side effects, nursing interventions such as turning and suctioning, and excessive ICU noise and light [9]. Thus, improving the patient's tolerance of these common issues that contribute to a state of relative discomfort or outright distress is important [9-13].Analgesia and sedation management has routinely been employed in ICU patients for many years, particularly among those receiving mechanical ventilation [14]. Surveys of ICU practitioners indicate continued widespread use and provide insight into the diversity of approaches, including the relative frequency with which specific medications are utilized and variability in monitoring, protocol use, and other clinical practice parameters [15-25]. An international cohort study of mechanically ventilated adults conducted in 1998 [26] (48% from Europe, 24% from Latin America, and 28% from North America) provides an instructive global composite of clinical practice. Only 68% of pa
Consensus guidelines on analgesia and sedation in dying intensive care unit patients
Laura A Hawryluck, William RC Harvey, Louise Lemieux-Charles, Peter A Singer
BMC Medical Ethics , 2002, DOI: 10.1186/1472-6939-3-3
Abstract: Using the Delphi technique, panelists rated levels of agreement with statements describing how analgesics and sedatives should be given to dying ICU patients and how palliative care should be distinguished from euthanasia. Participants were drawn from 3 panels: 1) Canadian Academic Adult Intensive Care Fellowship program directors and Intensive Care division chiefs (N = 9); 2) Deputy chief provincial coroners (N = 5); 3) Validation panel of Intensivists attending the Canadian Critical Care Trials Group meeting (N = 12).After three Delphi rounds, consensus was achieved on 16 statements encompassing the role of palliative care in the intensive care unit, the management of pain and suffering, current areas of controversy, and ways of improving palliative care in the ICU.Consensus guidelines were developed to guide the administration of analgesics and sedatives to dying ICU patients and to help distinguish palliative care from euthanasia.Intensivists are confronted with a difficult balance in providing analgesia and sedation for dying patients. If they administer too little to control distress, they provide inadequate palliative care and patients suffer [1-7]. If they administer too much for life to continue, they may risk prosecution for committing euthanasia [6,8-15]. With recently increasing legal scrutiny, fear of prosecution may continue to grow and perpetuate the undertreatment of pain and suffering at the end of life [1-3], [7-16].The alleviation of pain and suffering is crucial to the provision of quality end-of-life Care [17]. While the US Society for Critical Care Medicine (SCCM) has published practice parameters[18] for the provision of analgesia and sedation in critically ill ICU patients, no guidelines exist for analgesic and sedative use in dying patients. In Canada, the Chief Coroner of Ontario has defined palliative care [19] to help coroners distinguish palliative care from euthanasia; however, these guidelines are not specific to the ICU and give no sp
Remifentanil for analgesia-based sedation in the intensive care unit
Ralf Kuhlen, Christian Putensen
Critical Care , 2003, DOI: 10.1186/cc2421
Abstract: Providing effective analgesia and adequate sedation is a generally accepted goal in the intensive care unit (ICU). Most critically ill patients – especially those who are mechanically ventilated – are treated with various analgesics and sedative drugs, which have primarily been investigated for their short-term use for anaesthesia during surgical interventions. Recent studies suggest that longer term administration of these drugs might be associated with significant risks and adverse effects. Therefore, we must learn that their use has to undergo a risk–benefit assessment as strict as is required for other treatments.In this issue of Critical Care two investigations further promote our understanding of analgesics and sedatives in critically ill patients by investigating the use of remifentanil for analgesia-based sedation protocols in the ICU setting [1,2].Breen and colleagues [2] investigated the clinical effects of continuous remifentanil infusion for up to 72 hours supplemented by propofol in ICU patients with impaired or normal renal function. They found that scheduled down-titrations of the remifentanil infusion at 8, 24, 48 and 72 hours resulted in statistically significant but clinically irrelevant differences in time to offset of sedative effect, as assessed on the basis of clinical signs. This observation in an ICU setting substantiates data suggesting that remifentanil clearance is clinically independent of renal function because of its esterase dependent metabolism [3]. The metabolite remifentanil acid is known to accumulate in renal failure [3], but because this metabolite is approximately 1/4600 less potent than remifentanil [4] this should not result in any clinical effect. This hypothesis was supported by Breen and colleagues [2], who found no correlation between remifentanil acid and time to offset of analgesic and sedative effects in patients with renal dysfunction. No differences in adverse events related to the study drug were found, although the
Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308]
Andreas Karabinis, Kostas Mandragos, Spiros Stergiopoulos, Apostolos Komnos, Jens Soukup, Ben Speelberg, Andrew JT Kirkham
Critical Care , 2004, DOI: 10.1186/cc2896
Abstract: Patients aged 18–80 years admitted to the intensive care unit within the previous 24 hours, with acute brain injury or after neurosurgery, intubated, expected to require mechanical ventilation for 1–5 days and requiring daily downward titration of sedation for assessment of neurological function were studied. Patients received one of two treatment regimens. Regimen one consisted of analgesia-based sedation, in which remifentanil (initial rate 9 μg kg-1 h-1) was titrated before the addition of a hypnotic agent (propofol [0.5 mg kg-1 h-1] during days 1–3, midazolam [0.03 mg kg-1 h-1] during days 4 and 5) (n = 84). Regimen two consisted of hypnotic-based sedation: hypnotic agent (propofol days 1–3; midazolam days 4 and 5) and fentanyl (n = 37) or morphine (n = 40) according to routine clinical practice. For each regimen, agents were titrated to achieve optimal sedation (Sedation–Agitation Scale score 1–3) and analgesia (Pain Intensity score 1–2).Overall, between-patient variability around the time of neurological assessment was statistically significantly smaller when using remifentanil (remifentanil 0.44 versus fentanyl 0.86 [P = 0.024] versus morphine 0.98 [P = 0.006]. Overall, mean neurological assessment times were significantly shorter when using remifentanil (remifentanil 0.41 hour versus fentanyl 0.71 hour [P = 0.001] versus morphine 0.82 hour [P < 0.001]). Patients receiving the remifentanil-based regimen were extubated significantly faster than those treated with morphine (1.0 hour versus 1.93 hour, P = 0.001) but there was no difference between remifentanil and fentanyl. Remifentanil was effective, well tolerated and provided comparable haemodynamic stability to that of the hypnotic-based regimen. Over three times as many users rated analgesia-based sedation with remifentanil as very good or excellent in facilitating assessment of neurological function compared with the hypnotic-based regimen.Analgesia-based sedation with remifentanil permitted significantly
Pediatric procedural sedation and analgesia
Meredith James,O′Keefe Kelly,Galwankar Sagar
Journal of Emergencies, Trauma and Shock , 2008,
Abstract: Procedural sedation and analgesia (PSA) is an evolving field in pediatric emergency medicine. As new drugs breach the boundaries of anesthesia in the Pediatric Emergency Department, parents, patients, and physicians are finding new and more satisfactory methods of sedation. Short acting, rapid onset agents with little or no lingering effects and improved safety profiles are replacing archaic regimens. This article discusses the warning signs and areas of a patient′s medical history that are particularly pertinent to procedural sedation and the drugs used. The necessary equipment is detailed to provide the groundwork for implementing safe sedation in children. It is important for practitioners to familiarize themselves with a select few of the PSA drugs, rather than the entire list of sedatives. Those agents most relevant to PSA in the pediatric emergency department are presented.
Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomised trial [ISRCTN47583497]
Des Breen, Andreas Karabinis, Manu Malbrain, Rex Morais, Sven Albrecht, Inge-Lise Jarnvig, Pauline Parkinson, Andrew JT Kirkham
Critical Care , 2005, DOI: 10.1186/cc3495
Abstract: One hundred and five randomised patients received either a remifentanil-based sedation regime (initial dose 6 to 9 μg kg-1 h-1 (0.1 to 0.15 μg kg-1 min-1) titrated to response before the addition of midazolam for further sedation (n = 57), or a midazolam-based sedation regime with fentanyl or morphine added for analgesia (n = 48). Patients were sedated to an optimal Sedation–Agitation Scale (SAS) score of 3 or 4 and a pain intensity (PI) score of 1 or 2.The remifentanil-based sedation regime significantly reduced the duration of mechanical ventilation by more than 2 days (53.5 hours, P = 0.033), and significantly reduced the time from the start of the weaning process to extubation by more than 1 day (26.6 hours, P < 0.001). There was a trend towards shortening the stay in the intensive care unit (ICU) by 1 day. The median time of optimal SAS and PI was the same in both groups. There was a significant difference in the median time to offset of pharmacodynamic effects when discontinuing study medication in patients not extubated at 10 days (remifentanil 0.250 hour, comparator 1.167 hours; P < 0.001). Of the patients treated with remifentanil, 26% did not receive any midazolam during the study. In those patients that did receive midazolam, the use of remifentanil considerably reduced the total dose of midazolam required. Between days 3 and 10 the weighted mean infusion rate of remifentanil remained constant with no evidence of accumulation or of a development of tolerance to remifentanil. There was no difference between the groups in SAS or PI score in the 24 hours after stopping the study medication. Remifentanil was well tolerated.Analgesia-based sedation with remifentanil was well tolerated; it reduces the duration of mechanical ventilation and improves the weaning process compared with standard hypnotic-based sedation regimes in ICU patients requiring long-term ventilation for up to 10 days.Most patients who require intensive care need effective analgesia and sedat
Bispectral index versus COMFORT score to determine the level of sedation in paediatric intensive care unit patients: a prospective study
Andreas E Triltsch, Grit Nestmann, Helmut Orawa, Maryam Moshirzadeh, Michael Sander, Joachim Gro?e, Arka Gen?hr, Wolfgang Konertz, Claudia D Spies
Critical Care , 2004, DOI: 10.1186/cc2977
Abstract: Forty paediatric patients (<18 years) were sedated for mechanical ventilation in a cardiac surgical and general PICU. In each paediatric patient BIS and COMFORT score were obtained. The study protocol did not influence ongoing PICU therapy. BIS and corresponding COMFORT score were collected three times for each patient. Measurements with the best starting EEG impedances were analyzed further. Deep sedation was defined as a COMFORT score between 8 and 16, and light sedation as a score between 17 and 26. Biometric and physiological data, and Pediatric Risk of Mortality III scores were also recorded.There was a good correlation (Spearman's rho 0.651; P = 0.001) between BIS and COMFORT score in the presence of deep sedation and low starting impedance. Receiver operating characteristic (ROC) analysis revealed best discrimination between deep and light sedation at a BIS level of 83.In the presence of deep sedation, BIS correlated satisfactorily with COMFORT score results if low EEG impedances were guaranteed.Most paediatric intensive care unit (ICU) patients need sedative and analgesic drugs during mechanical ventilation [1]. Sedatives and analgesics are given to improve comfort, to reduce pain, to facilitate aggressive ICU therapy (i.e. mechanical ventilation or insertion of intravascular lines) and to avoid accidental removal of medical devices. Most clinicians give sedatives and analgesics according to their professional experience and the patient's estimated need for sedation. Inadequate monitoring of sedation and analgesia may contribute to adverse outcomes and complications [2].Only a few clinical scores have been validated for estimating the level of sedation in paediatric ICU patients. The best evaluated score is the COMFORT score [3]. The COMFORT score consists of eight categories and can evaluate a child's behaviour and physiological responses to discomfort, fear and pain in approximately 2 min. The COMFORT score is age independent because age-adapted physiologi
Sedation and Analgesia in Intensive Care: A Comparison of Fentanyl and Remifentanil  [PDF]
F. Cevik,M. Celik,P. M. Clark,C. Macit
Pain Research and Treatment , 2011, DOI: 10.1155/2011/650320
Abstract: Optimal sedation and analgesia are of key importance in intensive care. The aim of this study was to assess the quality of sedoanalgesia and outcome parameters in regimens containing midazolam and either fentanyl or remifentanil. A prospective, randomized, open-label, controlled trial was carried out in the ICU unit of a large teaching hospital in Istanbul over a 9-month period. Thirty-four patients were randomly allocated to receive either a remifentanil-midazolam regimen (R group, ) or a fentanyl-midazolam regimen (F group, ). A strong correlation between Riker Sedation-Agitation Scale (SAS) and Ramsey Scale (RS) measurements was observed. Comparatively, remifentanil provided significantly more potent and rapid analgesia based on Behavioral-Physiological Scale (BPS) measurements and a statistically nonsignificantly shorter time to discharge. On the other hand, remifentanil also caused a significantly sharper fall in heart rate within the first six hours of treatment. 1. Introduction Virtually every patient admitted into ICU is administered analgesia and sedation therapy. Therefore, sedation and pain control are crucial in the management of intensive care unit (ICU) patients. Because of the multiplicity of patients admitted to ICU, it is difficult to define a standard procedure for ICU sedation. One may encounter a variety of pathologies of different grades of severity; in addition, the associated morbidity, the circulatory instability, and the pharmacodynamic alterations in critically ill patients can make treatment guideline difficult to establish and implement [1]. Precise control of the depth of sedation is often not well managed; patients are frequently over- or undersedated with an accompanying increase in morbidity, mortality, and economic cost. The provision of effective analgesia and sedation for patients in ICU is important in controlling pain, dyspnea, and delirium; relieving agitation and anxiety; decreasing oxygen consumption; providing amnesia; preventing seizure; maintaining brain function; applying neuromuscular blockage; aiding compliance with mechanical ventilation; thereby maintaining patient comfort [2–4]. Agents such as propofol and midazolam are commonly used for sedation in ICU because of their effectiveness and relatively short elimination half-lives. The risk for accumulation and delayed recovery with these agents appears to be lower than that with traditional opioids. Consequently, opioid dose is usually minimized, with clinicians choosing to manipulate the sedative dose to maintain optimal patient comfort. On the other hand,
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