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Sedation protocols versus daily sedation interruption: a systematic review and meta-analysis

ABSTRACT

Objective:

The aim of this study was to systematically review studies that compared a mild target sedation protocol with daily sedation interruption and to perform a meta-analysis with the data presented in these studies.

Methods:

We searched Medline, Scopus and Web of Science databases to identify randomized clinical trials comparing sedation protocols with daily sedation interruption in critically ill patients requiring mechanical ventilation. The primary outcome was mortality in the intensive care unit.

Results:

Seven studies were included, with a total of 892 patients. Mortality in the intensive care unit did not differ between the sedation protocol and daily sedation interruption groups (odds ratio [OR] = 0.81; 95% confidence interval [CI] 0.60 - 1.10; I2 = 0%). Hospital mortality, duration of mechanical ventilation, intensive care unit and hospital length of stay did not differ between the groups either. Sedation protocols were associated with an increase in the number of days free of mechanical ventilation (mean difference = 6.70 days; 95%CI 1.09 - 12.31 days; I2 = 87.2%) and a shorter duration of hospital length of stay (mean difference = -5.05 days, 95%CI -9.98 - -0.11 days; I2 = 69%). There were no differences in regard to accidental extubation, extubation failure and the occurrence of delirium.

Conclusion:

Sedation protocols and daily sedation interruption do not appear to differ in regard to the majority of analyzed outcomes. The only differences found were small and had a high degree of heterogeneity.

Keywords:
Conscious sedation; Clinical protocols; Respiration, artificial; Critical care

RESUMO

Objetivo:

Revisar, de forma sistemática, os estudos que compararam um protocolo com alvo de sedação leve e a interrupção diária da sedação, bem como realizar uma metanálise com os dados apresentados nestes estudos.

Métodos:

Foram realizadas buscas nas bases de dados Medline, Scopus e Web of Science para a identificação estudos clínicos randomizados que compararam protocolos de sedação com a interrupção diária da sedação em pacientes críticos com necessidade de ventilação mecânica. O desfecho primário analisado foi mortalidade na unidade de terapia intensiva.

Resultados:

Foram incluídos 7 estudos, com total de 892 pacientes. A mortalidade na unidade de terapia intensiva não foi diferente entre os grupos protocolo de sedação ou interrupção diária da sedação (OR = 0,81; IC 95% 0,60 - 1,10; I2 = 0%). Mortalidade hospitalar, duração da ventilação mecânica e da internação na unidade de terapia intensiva também não foram diferentes dentre os grupos. Os protocolos de sedação associaram-se a um aumento do número de dias livres de ventilação mecânica (diferença média = 6,70 dias; IC95% 1,09 - 12,31 dias; I2 = 87,2%). Os protocolos de sedação associaram-se a uma menor duração da internação hospitalar (diferença média = -5,05 dias; IC 95% -9,98 - -0,11 dias; I2 = 69%). Não houve diferenças quanto à extubação acidental, à falha de extubação e à ocorrência de delirium.

Conclusão:

Protocolos de sedação e interrupção diária da sedação não parecem diferentes quanto à maioria dos desfechos analisados. As diferenças encontradas foram pequenas e com um elevado grau de heterogeneidade.

Descritores:
Sedação consciente; Protocolos clínicos; Respiração artificial; Cuidados críticos

INTRODUCTION

Proper sedation is an important component in the care of critically ill patients requiring mechanical ventilation. Deep sedation levels are associated with several negative outcomes, such as increased time on mechanical ventilation,(11 Kollef MH, Levy NT, Ahrens TS, Schaiff R, Prentice D, Sherman G. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest. 1998;114(2):541-8.) delirium,(22 Ouimet S, Riker R, Bergeron N, Cossette M, Kavanagh B, Skrobik Y. Subsyndromal delirium in the ICU: evidence for a disease spectrum. Intensive Care Med. 2007;33(6):1007-13.) memory disturbances,(33 Costa JB, Marcon SS, Macedo CR, Jorge AC, Duarte PA. Sedation and memories of patients subjected to mechanical ventilation in an intensive care unit. Rev Bras Ter Intensiva. 2014;26(2):122-9.) and higher mortality in the short(44 Tanaka LM, Azevedo LC, Park M, Schettino G, Nassar AP, Réa-Neto A, Tannous L, de Souza-Dantas VC, Torelly A, Lisboa T, Piras C, Carvalho FB, Maia Mde O, Giannini FP, Machado FR, Dal-Pizzol F, de Carvalho AG, dos Santos RB, Tierno PF, Soares M, Salluh JI; ERICC study investigators. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study. Crit Care. 2014;18(4):R156.) and long term.(55 Balzer F, Weiss B, Kumpf O, Treskatsch S, Spies C, Wernecke KD, et al. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care. 2015;19:197.)

The deleterious effects of deep sedation can be minimized by employing a strategy of sedation protocols that target lighter sedation levels(66 Ranzani OT, Simpson ES, Augusto TB, Cappi SB, Noritomi DT; AMIL Critical Care Group. Evaluation of a minimal sedation protocol using ICU sedative consumption as a monitoring tool: a quality improvement multicenter project. Crit Care. 2014;18(5):580.,77 Bugedo G, Tobar E, Aguirre M, Gonzalez H, Godoy J, Lira MT, et al. The implementation of an analgesia-based sedation protocol reduced deep sedation and proved to be safe and feasible in patients on mechanical ventilation. Rev Bras Ter Intensiva. 2013;25(3):188-96.) and the daily interruption of sedative infusion.(88 Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-7.,99 Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. 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. Lancet. 2008;371(9607):126-34.) The effects of these strategies have been assessed in two systematic reviews in which the included study control groups consisted of patients who received "usual" care in relation to the sedation of patients on mechanical ventilation. The first systematic review that included observational and randomized studies showed that most of the studies suggested a reduction in the duration of mechanical ventilation and ICU and hospital length of stay.(1010 Jackson DL, Proudfoot CW, Cann KF, Walsh T. A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety. Crit Care. 2010;14(2):R59.) The second systematic review included only randomized studies and pooled their results into a meta-analysis, which indicated that there were reduced ICU and hospital length of stay and reduced mortality with the use of both sedation reduction strategies.(1111 Minhas MA, Velasquez AG, Kaul A, Salinas PD, Celi LA. Effect of protocolized sedation on clinical outcomes in mechanically ventilated intensive care unit patients: a systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(5):613-23.) Another meta-analysis also suggested that the two sedation minimization strategies were not associated with higher incidences of post-traumatic stress in the long term,(1212 Nassar AP Jr, Zampieri FG, Ranzani OT, Park M. Protocolized sedation effect on post-ICU posttraumatic stress disorder prevalence: A systematic review and network meta-analysis. J Crit Care. 2015;30(6):1278-82.) which was a fear that had been raised when the first study on daily sedation interruption was published.(1313 Heffner JE. A wake-up call in the intensive care unit. N Engl J Med. 2000;342(20):1520-2.)

Therefore, protocols targeting either a light sedation level or daily sedative infusion interruption should be adopted to reduce the deleterious effects of excessive sedation.(1414 Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263-306. Review.) However, the use of these strategies is still far from universal,(1515 Shinotsuka CR, Salluh JI. Perceptions and practices regarding delirium, sedation and analgesia in critically ill patients: a narrative review. Rev Bras Ter Intensiva. 2013;25(2):155-61.) and it is unclear whether one of the two is more effective than the other.

The objective of this study was to systematically review studies that compared a light target sedation protocol with daily sedation interruption.

METHODS

Search strategy

Searches of the Medline (via PubMed), Scopus and Web of Science databases were performed. The studies were obtained by combining the following keywords: ("sedation" OR "sedatives") AND ("critical care" OR "intensive care" OR "critically ill") AND ("daily interruption"). Additional studies were sought based on the references of included studies and personal files. There was no language restriction. The searches were limited to randomized clinical studies performed on adults and published up to February 4, 2016. Titles and abstracts were assessed for eligibility. The full texts of potentially relevant articles were analyzed. The eligibility assessment was conducted by the authors, and disagreements were resolved by consensus. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used as a guide.(1616 Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;349:g7647.) The systematic review was recorded in the PROSPERO database (CRD 42014014121). As the study is a literature review, there was no need for Ethics Committee approval.

Study selection

Studies that met the following criteria were included: those comparing a protocol with a predefined sedation scale target with daily sedative infusion interruption; and those assessing any of the following outcomes: mortality in intensive care, duration of mechanical ventilation, days free of mechanical ventilation in 28 days and ICU length of stay.

Data extraction

The authors extracted the following data independently using a specific form: country where the study was conducted, year of publication, study design, number of patients included in each study group, description of the sedation protocol and the manner in which daily sedation interruption was conducted, ICU and hospital mortality, duration of mechanical ventilation, days free of mechanical ventilation in 28 days, ICU and hospital length of ICU stay, delirium, accidental extubation rates and extubation failure (reintubation within 48 hours). Authors of included studies were contacted by e-mail to obtain information about missing data from the publications.

Evaluation of study quality

Study quality was assessed by the Cochrane risk of bias assessment tool for clinical studies. The risk of bias was assessed as "low", "uncertain" or "high" in the following areas: generation of random sequence, allocation concealment, blinding of participants and professionals, blinding of outcome assessors, incomplete outcomes, selective outcome reporting, and other sources of bias. Disagreements were resolved by consensus.

Outcomes

The primary outcome was mortality in the ICU. Secondary outcomes were duration of mechanical ventilation, days free of mechanical ventilation in 28 days, hospital mortality, ICU and hospital length of stay, prevalence of delirium, and accidental extubation and extubation failure rates (reintubation within 48 hours after extubation).

Statistical analysis

A random effects model was used due to the variability among studies regarding samples and how the interventions were applied. The differences between groups were expressed as odds ratios (OR) for categorical variables and as mean differences (MD) for continuous variables, both with 95% confidence intervals (95%CI). The reference group for the analysis was always "sedation protocol." Heterogeneity was assessed using the I2 statistic and was classified as low (< 25%), moderate (25 - 50%) or high (> 50%). The analyses were performed using R software version 3.3.1, with R Studio version 0.99.902, and the meta package (version 4.4.0) developed by Guido Schwazer (http://cran.rproject.org/web/packages/meta/meta.pdf).

RESULTS

Study characteristics

A total of 279 references were identified by the search strategies, eight full-text articles were assessed for eligibility. In total, seven studies(1717 Mehta S, Burry L, Martinez-Motta JC, Stewart TE, Hallett D, McDonald E, Clarke F, Macdonald R, Granton J, Matte A, Wong C, Suri A, Cook DJ; Canadian Critical Care Trials Group. A randomized trial of daily awakening in critically ill patients managed with a sedation protocol: a pilot trial. Crit Care Med. 2008;36(7):2092-9.

18 de Wit M, Gennings C, Jenvey WI, Epstein SK. Randomized trial comparing daily interruption of sedation and nursing-implemented sedation algorithm in medical intensive care unit patients. Crit Care. 2008;12(3):R70.

19 Anifantaki S, Prinianakis G, Vitsaksaki E, Katsouli V, Mari S, Symianakis A, et al. Daily interruption of sedative infusions in an adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs. 2009;65(5):1054-60.

20 Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-80.

21 Yiliaz C, Kelebek Girgin N, Ozdemir N, Kutlay O. The effect of nursing-implemented sedation on the duration of mechanical ventilation in the ICU. Ulus Travma Acil Cerrahi Derg. 2010;16(6):521-6.

22 Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, Herridge M, Ferguson N, Devlin J, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Skrobik Y, Hébert P, Sabri E, Meade M; SLEAP Investigators.; Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308(19):1985-92. Erratum in: JAMA. 2013;309(3):237.
-2323 Nassar Junior AP, Park M. Daily sedative interruption versus intermittent sedation in mechanically ventilated critically ill patients: a randomized trial. Ann Intensive Care. 2014;4:14.) were included; one was excluded, as it did not report any of the outcomes of interest(2424 Bassuoni AS, Elgebaly AS, Eldabaa AA, Elhafz AA. Patient-ventilator asynchrony during daily interruption of sedation versus no sedation protocol. Anesth Essays Res. 2012;6(2):151-6.) (Figure 1).

Figure 1
Study flowchart.

The characteristics of the included studies are described in table 1. In general, the studies were small, and only one was a multicenter study. The goal was light to moderate sedation in all studies. The Sedation-Agitation Scale (SAS), the Ramsay scale and the Richmond Agitation Sedation Scale (RASS) were used in three, three and two studies, respectively. Only one of the studies had a deeper sedation level as its lower target (Ramsay 5).(1919 Anifantaki S, Prinianakis G, Vitsaksaki E, Katsouli V, Mari S, Symianakis A, et al. Daily interruption of sedative infusions in an adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs. 2009;65(5):1054-60.) Descriptions of the sedation protocols and daily sedation interruption can be found in table 2.

Table 1
Study characteristics
Table 2
Sedation protocol and daily interruption performed in each study

Quality assessment

Generally, all studies had a low risk of bias, except for the blinding of participants and professionals, which was absent in all studies. The risk of bias was considered "uncertain" for the blinding of outcome assessors, as they could know into which sedation strategy patients were randomized. This risk was considered uncertain because the analyzed outcomes were goals (e.g., mortality) or because this assessment was not described in the study. Allocation concealment was not adequately described in one study;(1919 Anifantaki S, Prinianakis G, Vitsaksaki E, Katsouli V, Mari S, Symianakis A, et al. Daily interruption of sedative infusions in an adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs. 2009;65(5):1054-60.) thus, the risk of bias was considered "uncertain" (Table 3).

Table 3
Risk of bias assessment

Outcomes

ICU mortality was assessed in seven studies with a total of 892 patients. There were no differences in ICU mortality between the sedation protocol and daily sedation interruption groups (OR = 0.81, 95% CI 0.60 - 1.10; I2 = 0%) (Figure 2). Hospital mortality was assessed in six studies, with a total of 832 patients. There were no differences in hospital mortality between the sedation protocol and daily sedation interruption groups (OR = 0.89, 95% CI 0.66 - 1.19; I2 = 0%) (Figure 1S - http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf).

Figure 2
Mortality in the intensive care unit.

OR - odds ratio; 95%CI: 95% confidence interval; W - weight of study.


The duration of mechanical ventilation was assessed in 6 studies, which included 769 patients. The sedation protocols were not associated with any reduction in the duration of mechanical ventilation when compared to daily sedation interruption (MD = -1.52 days, 95%CI -3.60 - 0.56 days; I2 = 86.1%) (Figure 3). Three studies, totaling 266 patients, analyzed the free days of mechanical ventilation in 28 days. The sedation protocols were associated with an increase free days of mechanical ventilation, but this result was marked by significant heterogeneity (MD = 6.70 days; 95%CI 1.09 - 12.31 days; I2 = 87.2%) (Figure 2S - http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf).

Figure 3
Time on mechanical ventilation.

SD - standard deviation; MD - mean difference; 95%CI - 95% confidence interval; W - weight of study.


Intensive care unit length of stay was assessed in six studies, including 769 patients. Hospital length of stay was also assessed in six studies and included 851 patients. There were no differences in the duration of ICU length of stay between the sedation protocols and daily sedation interruption (MD = -2.41 days, 95%CI -6.37 - 1.54 days; I2 = 89.9%) (Figure 3S - http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf). However, the sedation protocols were associated with a shorter duration of hospital length of stay (MD = -5.05 days, 95%CI -9.98 - -0.11 days, I2 = 69%) (Figure 4S - http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf).

Accidental extubation and extubation failure were assessed in four studies, involving 661 patients. The sedation protocols were not associated with higher rates of accidental extubation (OR = 1.02, 95%CI 0.55 to 1.90; I2 = 0%) (Figure 5S- http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf) or extubation failure (OR = 0.64, 95%CI 0.36 - 1.14; I2 = 0%) (Figure 6S-. http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf) compared to daily sedation interruption. The occurrence of delirium was assessed in only three studies, for a total of 596 patients. Delirium was not more common in patients allocated to sedation protocols than in those allocated to daily sedation interruption (OR = 1.45, 95%CI 0.77 - 2.73; I2 = 42.6%) (Figure 7S - http://www.rbti.org.br/content/imagebank/pdf/0103-507X-rbti-28-04-0444-suppl01-en.pdf).

DISCUSSION

This systematic review and meta-analysis suggests that there are no differences between sedation protocols that target light sedation levels and daily sedation interruption strategies regarding mortality, duration of mechanical ventilation and length of ICU stay. With the use of sedation protocols targeting lighter levels of sedation, the number of free days of mechanical ventilation was higher and the hospital stay was shorter. However, these findings were based on a small number of studies, in the case of time free of mechanical ventilation, and were marked by high heterogeneity within the two results.

The minimization of sedation is imperative when considering the deleterious effects of excessive sedation.(44 Tanaka LM, Azevedo LC, Park M, Schettino G, Nassar AP, Réa-Neto A, Tannous L, de Souza-Dantas VC, Torelly A, Lisboa T, Piras C, Carvalho FB, Maia Mde O, Giannini FP, Machado FR, Dal-Pizzol F, de Carvalho AG, dos Santos RB, Tierno PF, Soares M, Salluh JI; ERICC study investigators. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study. Crit Care. 2014;18(4):R156.,55 Balzer F, Weiss B, Kumpf O, Treskatsch S, Spies C, Wernecke KD, et al. Early deep sedation is associated with decreased in-hospital and two-year follow-up survival. Crit Care. 2015;19:197.) Sedation protocols(2525 Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, et al. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;27(12):2609-15.) and daily sedation interruption(88 Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-7.) have been studied for over 15 years and have shown significant benefits in terms of outcomes(1010 Jackson DL, Proudfoot CW, Cann KF, Walsh T. A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety. Crit Care. 2010;14(2):R59.,1111 Minhas MA, Velasquez AG, Kaul A, Salinas PD, Celi LA. Effect of protocolized sedation on clinical outcomes in mechanically ventilated intensive care unit patients: a systematic review and meta-analysis of randomized controlled trials. Mayo Clin Proc. 2015;90(5):613-23.) and safety with respect to adverse events, such as accidental extubation, extubation failure(99 Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. 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. Lancet. 2008;371(9607):126-34.,2525 Brook AD, Ahrens TS, Schaiff R, Prentice D, Sherman G, Shannon W, et al. Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med. 1999;27(12):2609-15.) and long-term psychological outcomes.(1212 Nassar AP Jr, Zampieri FG, Ranzani OT, Park M. Protocolized sedation effect on post-ICU posttraumatic stress disorder prevalence: A systematic review and network meta-analysis. J Crit Care. 2015;30(6):1278-82.) The results of our meta-analysis do not suggest significant differences between the two approaches in regard to important outcomes. In addition, our meta-analysis suggests low occurrences of accidental extubation and extubation failure, which are two common fears when addressing sedation reduction strategies.(2626 Tanios MA, de Wit M, Epstein SK, Devlin JW. Perceived barriers to the use of sedation protocols and daily sedation interruption: a multidisciplinary survey. J Crit Care. 2009;24(1):66-73.,2727 Rose L, Fitzgerald E, Cook D, Kim S, Steinberg M, Devlin JW, Ashley BJ, Dodek P, Smith O, Poretta K, Lee Y, Burns K, Harvey J, Skrobik Y, Fergusson D, Meade M, Kraguljac A, Burry L, Mehta S; SLEAP Investigators; Canadian Critical Care Trials Group. Clinician perspectives on protocols designed to minimize sedation. J Crit Care. 2015;30(2):348-52.)

Another meta-analysis that aimed to assess the effectiveness of daily sedation interruption conducted a sub-analysis that compared it with the use of sedation protocols with regard to the duration of mechanical ventilation. The comparison also revealed no differences between the two approaches regarding this outcome.(2828 Burry L, Rose L, McCullagh IJ, Fergusson DA, Ferguson ND, Mehta S. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Cochrane Database Syst Rev. 2014;(7):CD009176.) Our meta-analysis included two studies that were not included by this other review. Anifantaki et al.'s study(1919 Anifantaki S, Prinianakis G, Vitsaksaki E, Katsouli V, Mari S, Symianakis A, et al. Daily interruption of sedative infusions in an adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs. 2009;65(5):1054-60.) was excluded because the authors considered that the protocol group represented "usual care" of the unit where the study was conducted. Unlike the Cochrane review, we decided to include the first study because the protocol effectively describes targeting a light sedation level.(1919 Anifantaki S, Prinianakis G, Vitsaksaki E, Katsouli V, Mari S, Symianakis A, et al. Daily interruption of sedative infusions in an adult medical-surgical intensive care unit: randomized controlled trial. J Adv Nurs. 2009;65(5):1054-60.) In our opinion, "usual care" refers to the decision of the unit to infuse sedatives according to physician's orders and without set targets, as effectively occurred in the other studies included(88 Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med. 2000;342(20):1471-7.,99 Girard TD, Kress JP, Fuchs BD, Thomason JW, Schweickert WD, Pun BT, et al. 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. Lancet. 2008;371(9607):126-34.,2929 Weisbrodt L, McKinley S, Marshall AP, Cole L, Seppelt IM, Delaney A. Daily interruption of sedation in patients receiving mechanical ventilation. Am J Crit Care. 2011;20(4):e90-8.) and in the other meta-analysis.(2828 Burry L, Rose L, McCullagh IJ, Fergusson DA, Ferguson ND, Mehta S. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Cochrane Database Syst Rev. 2014;(7):CD009176.) Strom et al.'s study(2020 Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-80.) was excluded because the authors contemplated interruption of sedation in both groups. However, we decided to include this study because daily sedation interruption became part of the protocol only for patients who were still uncomfortable after administration of haloperidol and four attempts to suspend propofol infusion, used to control agitation.(2020 Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-80.) Therefore, we considered that sedation interruption was part of the protocol and not the protocol itself, as occurred in the other group.

Despite the apparent equivalence of daily sedation interruption and the protocols regarding outcomes and safety, three additional factors should be addressed. The first and foremost factor refers to nursing workload. While one of the studies included in this meta-analysis suggested the need for one professional more per patient to meet the demands of the same in the sedation protocol group,(2020 Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475-80.) a Brazilian study showed no differences in nursing workload between groups during the first five days of mechanical ventilation.(2323 Nassar Junior AP, Park M. Daily sedative interruption versus intermittent sedation in mechanically ventilated critically ill patients: a randomized trial. Ann Intensive Care. 2014;4:14.) The second factor relates to the expectations and preferences of the professionals responsible for patient care. While approval of the sedation protocol was similar for physicians and nurses who participated in another study included in the review,(2222 Mehta S, Burry L, Cook D, Fergusson D, Steinberg M, Granton J, Herridge M, Ferguson N, Devlin J, Tanios M, Dodek P, Fowler R, Burns K, Jacka M, Olafson K, Skrobik Y, Hébert P, Sabri E, Meade M; SLEAP Investigators.; Canadian Critical Care Trials Group. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308(19):1985-92. Erratum in: JAMA. 2013;309(3):237.) nurses' approval of daily sedation interruption was much lower than that of doctors. Nurses considered that the sedation protocol was easier to use and allowed greater patient comfort.(2727 Rose L, Fitzgerald E, Cook D, Kim S, Steinberg M, Devlin JW, Ashley BJ, Dodek P, Smith O, Poretta K, Lee Y, Burns K, Harvey J, Skrobik Y, Fergusson D, Meade M, Kraguljac A, Burry L, Mehta S; SLEAP Investigators; Canadian Critical Care Trials Group. Clinician perspectives on protocols designed to minimize sedation. J Crit Care. 2015;30(2):348-52.) The third factor relates to the experience and knowledge of a strategy, which, as would be expected, is associated with a greater likelihood of employing that strategy.(3030 Roberts RJ, de Wit M, Epstein SK, Didomenico D, Devlin JW. Predictors for daily interruption of sedation therapy by nurses: a prospective, multicenter study. J Crit Care. 2010;25(4):660.e1-7.)

The results of this meta-analysis should be interpreted with caution. Despite an extensive database search, only seven studies met the previously established inclusion criteria. Six of the seven studies were single-center and included few patients. Therefore, their results may not be valid in centers with different profiles. The variation in study characteristics is evident from the high statistical heterogeneity found in the analysis of outcomes involving time (i.e., duration of mechanical ventilation, ICU stay and hospital stay). Despite having a common target of sedation, both the protocols and the daily interruption strategy were performed differently from one study to another (Table 2), which could lead to discrepancies in results. We believe that data from ongoing studies (NCT01728558, NCT02040649) should shed more light on our findings in the coming years.

CONCLUSION

Sedation protocols and daily sedation interruption appear to be equivalent as strategies targeting lighter sedation levels, although it should be noted that the target of sedation should be the primary goal of management in most patients under mechanical ventilation.

  • Responsible editor: Jorge Ibrain de Figueira Salluh

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Publication Dates

  • Publication in this collection
    Oct-Dec 2016

History

  • Received
    30 June 2016
  • Accepted
    13 Aug 2016
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