Menoufia Medical Journal

REVIEW ARTICLE
Year
: 2020  |  Volume : 33  |  Issue : 2  |  Page : 339--345

Analgesia and sedation for patients in the intensive care unit: a systematic review


Nagwa M Doha1, Tarek A El-Henawy1, Moaaz M Mohammed2,  
1 Department of Anaesthesia, Intensive Care and Pain Management, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Anaesthesia, Intensive Care and Pain Management, Ministry of Health, Menoufia, Egypt

Correspondence Address:
Moaaz M Mohammed
Shebin El-Kom City, Menoufia Governorate
Egypt

Abstract

Objective To review the importance of sedation and analgesia in the ICU. Data sources A systematic search of MEDLINE (PubMed, Medscape, ScienceDirect, EMF-Portal) and internet was conducted on all articles published from 1974 to 2016. Study selection English language reports on the importance of sedation and analgesia in the ICU. The initial search presented 157 articles, where 23 had inclusion criteria. Data extraction Articles not reporting on the importance of sedation and analgesia in the ICU in the title or abstract were not included. Five independent investigators extracted data on the methods. Data synthesis Comparisons were made by a structured review with the results tabulated. Seven studies about the importance of the role of sedation and analgesia in the ICU, eight about assessing the adequacy of sedation, and eight about the strategies for administering sedatives in the ICU. Findings Pain perception varies according to the various factors including personality, cultural background, surroundings, and fear. It has been associated with the detrimental effects on sleep, agitation, and stress response. Anxiety is also brought about by continuous noise within the ICU. Patients in the ICU may also suffer from insomnia caused by a loss of normal melatonin secretion. Newer sedation scales are reported to show improvements in validity and reliability. Propofol may be associated with a more rapid wake-up than benzodiazepines. Conclusion Sedation is an important component of the treatment of mechanically ventilated, critically ill patients. Directing treatment to specific and individualized goals will assure that the patient needs are met. The use of a spontaneous waking trial, followed, when possible, by a spontaneous breathing trial, should be implemented widely in the care of critically ill patients requiring mechanical ventilation.



How to cite this article:
Doha NM, El-Henawy TA, Mohammed MM. Analgesia and sedation for patients in the intensive care unit: a systematic review.Menoufia Med J 2020;33:339-345


How to cite this URL:
Doha NM, El-Henawy TA, Mohammed MM. Analgesia and sedation for patients in the intensive care unit: a systematic review. Menoufia Med J [serial online] 2020 [cited 2020 Aug 4 ];33:339-345
Available from: http://www.mmj.eg.net/text.asp?2020/33/2/339/287801


Full Text



 Introduction



Critically ill patients require invasive monitoring and other support that may lead to anxiety, agitation, and pain[1]. Use of sedation is essential for the comfort and safety of these patients[2]. The primary goal of acute pain management in ICU patients are pain control and attenuation of the negative physiological and psychological consequences of unrelieved pain. However, a number of recent surveys have reported that enhanced pain management was associated with improved patient outcome in the ICU[3]. Because sedation is a dynamic process, it is often a balancing act to avoid suboptimal sedation and oversedation. Suboptimal sedation can place the patient at risk for physical stress such as unplanned estuationsor catheter removal and psychological stress such as anxiety, while oversedation increases the risks of hypoventilation, hypoxia, ventilator dependency, ventilator-associated pneumonia, increased length of ICU stays, and psychological sequelae[4]. Typical considerations include indication for sedation, onset duration of action, route of elimination, drug interactions, and adverse effects[5]. Cooperative sedation is a state in which the patient can be aroused from sedation without discontinuing the drug infusion, and when awake, the patients are able to communicate and follow commands. When arousal is no longer required, the patient is allowed to return to the prior state of sedation[6]. Cooperative sedation is associated with lower incidence of delirium and shorter ventilator time[7]. Assessment level of sedation and agitation is useful to titrate sedative medications and to evaluate agitated behavior[8]. The methods that are suitable for assessing the depth of sedation can be considered under two headings – objective or subjective assessment depending on whether the techniques require the application of an index that is derived from a quantifiable physiological variable (measurement system) or of a scoring system, respectively[9]. Many of the common complications of sedation in ICU patients are related to the patient-altered physiology and often have exaggerated known side effects (e.g., excessive hypotension, bradycardia, prolonged action, etc.). Sometimes, increasing doses are required as the patient develops tolerance to the drugs used. Some medications, like propofol, are known to be associated with specific fatal complications. Physically, the longer a patient stays sedated in the ICU the more likely they are to acquire complications such as lung atelectasis, secondary infection, thrombotic events, and even pressure sores due to their relative immobility. Patients who have prolonged stays may also develop muscle wasting and weakness, the so-called ICU myopathy/neuropathy syndrome[10]. The aim of this study was to review the importance of sedation and analgesia in the ICU.

 Materials and Methods



Data sources

A systematic search on the importance of sedation and analgesia in the ICU. Using MEDLINE (PubMed, Medscape, ScienceDirect, EMF-Portal) and internet was conducted on all articles published from 1974 to 2016. During the research that focused on the importance of sedation in the ICU/importance of analgesia in ICU/assessing adequacy of sedation/strategies for administering sedatives in the ICU were used as the search terms. Additional records were identified by reference lists in the retrieved articles. The search was established in the electronic databases from 1974 to 2016.

Study selection

Eligible articles were published in peer-reviewed journals and were written in English. Articles not reporting on the importance of sedation and analgesia in the ICU in the title or abstract were not included. Full-text articles were screened, and the final inclusion decisions were made according to the following criteria: original studies, systematic reviews, or meta-analyses; primary or first-line treatment and, if necessary, secondary treatment described, and treatment success, complications, and side-effects described.

Data extraction

Articles not reporting on the importance of sedation and analgesia in the ICU in the title or abstract were not included. Five independent investigators extracted data on the methods, health outcomes, and traditional protocol. There were surveys about symptoms and health without exposure assessment, report without peer-review, not within the national research program, and letters/comments/editorials/news and studies not focused on exposure from the prevalence of nocturnal enuresis.

The analyzed publications were evaluated according to evidence-based medicine (EBM) criteria using the classification of the US Preventive Services Task Force and UK National Health Service protocol for EBM in addition to the evidence pyramid.

US Preventive Services Task Force:

Level I: evidence obtained from at least one properly designed randomized controlled trialLevel II-1: evidence obtained from well-designed, controlled trials without randomizationLevel II-2: evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research groupLevel II-3: evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidenceLevel III: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Study quality assessment

Quality of all the studies was assessed. Important factors included the study design, ethical approval, calculation of evidence power, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that the confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.

Data synthesis

A structured, systematic review was done with the results tabulated. Seven studies about the role of terlipressin versus placebo in hepatorenal syndrome, eight about terlipressin versus noradrenaline, and eight about the adverse effects of terlipressin.

 Results



Study selection and characteristics

A systematic search on the role of sedation and analgesia in ICU using MEDLINE (PubMed, Medscape, ScienceDirect, EMF-Portal) and internet was conducted on all articles published from 1974 to 2016. Articles not reporting on the role of sedation and analgesia in the ICU in the title or abstract were not included. Five independent investigators extracted data on the methods, health outcomes, and traditional protocol. Potentially relevant publications were identified; 87 articles were excluded as they are away from our inclusion criteria. Twenty-three studies were reviewed as they met the inclusion criteria. Seven studies about the importance of the role of sedation and analgesia in the ICU, eight about assessing adequacy of sedation, and eight about strategies for administering sedatives in the ICU. Regarding these studies there were two prospective studies[11],[12] that come to level II-2 or level B, which comes in the second level regarding the pyramid of EBM. We found that patient–ventilator dyssynchrony or fighting the ventilator is a complex problem which is influenced by both ventilator performance and the patient. It is associated with adverse effects including increased work of breathing, patient discomfort, increased need for sedation, difficulties in weaning, prolongation of mechanical ventilation, longer stay in the ICU, and an increase in mortality. Also, four randomized control studies[13],[14],[15],[16] come to level I or level A reported that pain perception varies according to the various factors including personality, cultural background, surroundings, and fear. It has been associated with detrimental effects on sleep, agitation, and stress response. Anxiety is also brought about by continuous noise within the ICU such as monitoring machines, telephones, other patients, medical and nursing staff, and sleep deprivation which is a consequence of this noise. Twenty-four-hour lighting also contributes to anxiety. Furthermore, on a cohort analysis[17] comes in the second level regarding the pyramid of EBM and found that in cardiac surgery patients there is evidence supporting the use of intraoperative volatile agents for their direct myocardial protective properties and their use has been shown to reduce cardiac morbidity and mortality [Table 1]. Additionally, three randomized case–control studies[7],[18],[19] come to level I or level A found that assessing the adequacy of sedation can be difficult because of its subjective nature. Several objective sedation scales such as the Ramsay sedation scale and the sedation–agitation Scale have been developed. Also, three prospective studies[20],[21],[22] come to level II-2 or level B and found that the Ramsay scoring system is one of the most commonly used scales. Although it has the benefit of simplicity, it does not effectively measure the quality or degree of sedation with regard to the goals outlined above and has never been objectively validated, while two cohort analysis[8],[9] comes in the second level regarding the pyramid of EBM and found that the bispectral index monitor, a device that processes the raw electroencephalogram signal into a discrete scaled number, has been evaluated as a tool to monitor sedation in the ICU setting. Some have found this device to reliably detect a patient's level of consciousness under general anesthesia, although others have questioned the overall utility of this device for preventing awareness [Table 2]. Besides, one cohort study[17] comes in the second level regarding the pyramid of EBM and reported that the strategy of daily sedative interruption allowed a focused downward titration of sedative infusion rates over time, streamlining administration of these drugs, and minimizing the tendency for accumulation. Three randomized case–control studies[23],[24],[25] come to level I or level A, theses reported that previous studies have noted that propofol may be associated with a more rapid wake-up than benzodiazepines. The rapid recovery from propofol may be attenuated by concomitant administration of opiates for analgesia, however. Indeed, patients receiving prolonged administration of sedatives may develop tolerance and require escalating doses over time. Also, four cohort studies[4],[10],[11],[26] comes in the second level regarding the pyramid of EBM and reported that many established symptoms are either nonspecific or difficult to elicit from mechanically ventilated patients. It is clear that sedatives may impact the duration of mechanical ventilation. The reduction in the duration of mechanical ventilation that was observed by Brook and colleagues and us was likely related to earlier recognition of patient readiness to undergo spontaneous breathing trial. Others have reported previously an important link between a successful spontaneous breathing trial and subsequent liberation from mechanical ventilation [Table 3].{Table 1}{Table 2}{Table 3}

 Discussion



Patient–ventilator dyssynchrony or fighting the ventilator is a complex problem, which is influenced by both ventilator performance and the patient. It is associated with adverse effects including increased work of breathing, patient discomfort, increased need for sedation, difficulties in weaning, prolongation of mechanical ventilation, longer stay in the ICU, and an increase in mortality[11]. Pain perception varies according to various factors including personality, cultural background, surroundings, and fear. It has been associated with detrimental effects on sleep, agitation, and stress response. Failure to treat pain properly leads to an increased use of other sedative agents, increased sympathetic activity, and increased oxygen consumption. Furthermore, sleep disruption, sleep deprivation, and anxiety increase the perception of pain. Pain is commonly reported when ICU patients are reviewed following ICU discharge[13]. Anxiety is also brought about by continuous noise within ICU such as monitoring machines, telephones, other patients, medical and nursing staff, and sleep deprivation that is a consequence of this noise. Twenty-four-hour lighting also contributes to anxiety[14]. A protracted withdrawal syndrome may develop in some individuals with symptoms such as anxiety, irritability, insomnia, and sensory disturbances. In a small number of people, it can be severe and resemble serious psychiatric and medical conditions such as schizophrenia and seizure disorders. Withdrawal symptoms may persist for weeks or months after cessation of benzodiazepines. In a smaller subset of patient's, withdrawal symptoms may continue at a subacute level for many months or even years[15]. In cardiac surgery patients, there is evidence supporting the use of intraoperative volatile agents for their direct myocardial protective properties and their use has been shown to reduce cardiac morbidity and mortality[17]. Agitation is common in ICU patients who are not receiving mechanical ventilation. It is associated with a higher rate of self-removal of lines and catheters as well as a higher rate of hospital-acquired infection and a longer duration of hospital stay[16]. Patients in the ICU may also suffer from insomnia caused by a loss of normal melatonin secretion[16]. However, the primary factor causing sleep disruption is thought to be the ICU environment, noise from various sources including ventilators, monitor alarms, phones, and general noise of movements and personnel in the unit have all been reported to disrupt sleep[12]. Regarding, assessing adequacy of sedation can be difficult because of its subjective nature. Several objective sedation scales such as the Ramsay sedation scale[18] and the sedation–agitation Scale have been developed. The Ramsay scoring system is one of the most commonly used scales[7]. Although it has the benefit of simplicity, it does not effectively measure the quality or degree of sedation with regard to the goals outlined above[21] and has never been objectively validated[21]. Newer sedation scales are reported to show improvements in validity and reliability[7],[19]. The evaluation of sedation adequacy is a bedside maneuver. The nurse's input is critical, because he or she will often notice changes from an optimal level of sedation. Ideally, one would prefer a patient with all of the indications for sedation outlined above met, yet fully communicative with bedside caregivers. Such a state of sedation correlates with a Ramsay score of 2 or 3 or a sedation–agitation Scale score of 3 or 4[18]. The bispectral index monitor, a device that processes the raw electroencephalogram signal into a discrete scaled number, has been evaluated as a tool to monitor sedation in the ICU setting. Some have found this device to reliably detect a patient's level of consciousness under general anesthesia[8], although others have questioned the overall utility of this device for preventing awareness[9]. Although preliminary data in the ICU setting suggest a good correlation between the bispectral index and the sedation–agitation scale[22], this device has undergone limited evaluation in the ICU and awaits more extensive validation before its role in the ICU setting is established[22]. The strategy of daily sedative interruption allowed a focused downward titration of sedative infusion rates over time, streamlining administration of these drugs and minimizing the tendency for accumulation. Previous studies have noted that propofol may be associated with a more rapid wake-up than benzodiazepines. The rapid recovery from propofol may be attenuated by concomitant administration of opiates for analgesia, however. Indeed, patients receiving prolonged administration of sedatives may develop tolerance and require escalating doses over time[23]. Withdrawal symptoms may be seen in patients receiving prolonged infusions of sedatives. Katz's group noted a high incidence of withdrawal in infants receiving fentanyl in either high doses or for prolonged time periods[24]. Cammarano and colleagues noted a 32% incidence of withdrawal in adults receiving opiate, benzodiazepine, and propofol infusions. This tended to be associated with higher doses of these sedatives, with a trend toward occurrence with more rapid weaning of drugs[25]. The diagnosis of sedative or opiate withdrawal in critically ill ICU patients can be challenging. Many of the established signs of withdrawal (tachycardia, hypertension, fever, tachypnea, pupillary dilation, agitation, delirium, and seizures) are nonspecific, commonly observed phenomena in critically ill patients. Likewise, many established symptoms are either nonspecific or difficult to elicit from mechanically ventilated patients. It is clear that sedatives may impact the duration of mechanical ventilation[10],[26]. The reduction in the duration of mechanical ventilation that was observed by Brook and colleagues and us was likely related to earlier recognition of patient readiness to undergo a spontaneous breathing trial. Others have reported previously an important link between a successful spontaneous breathing trial and subsequent liberation from mechanical ventilation[4],[11]. Accordingly, we believe the use of a spontaneous waking trial, followed when possible by a spontaneous breathing trial, should be implemented widely in the care of critically ill patients requiring mechanical ventilation.

 Conclusion



This review found that sedation is an important component of the treatment of mechanically ventilated, critically ill patients. Directing treatment to specific and individualized goals will assure that patient needs are met. The use of a spontaneous waking trial, followed when possible by a spontaneous breathing trial, should be implemented widely in the care of critically ill patients requiring mechanical ventilation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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