What every intensivist should know about light sedation for mechanically ventilated patients

Lilian Maria Sobreira Tanaka Rodrigo Bernardo Serafim Jorge Ibrain Figueira Salluh About the authors

INTRODUCTION

Pain, agitation and anxiety are frequently experienced by patients requiring intensive care unit (ICU) admission. These events are often associated with tracheal intubation, mechanical ventilation (MV) and bedside procedures11 Puntillo KA, Max A, Timsit JF, Vignoud L, Chanques G, Robleda G, et al. Determinants of procedural pain intensity in the intensive care unit. The Europain(r) study. Am J Respir Crit Care Med. 2014;189(1):39-47.. Sedatives and analgesics can be used to minimize distress, ensure comfort, and decrease the work of breathing to achieve better synchrony with the ventilator.22 Arroliga AC, Thompson BT, Ancukiewicz M, Gonzales JP, Guntupalli KK, Park PK, Wiedemann HP, Anzueto A; Acute Respiratory Distress Syndrome Network. Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2008;36(4):1083-8. A number of landmark studies have been published in the past decade, improving our understanding about the choice of sedatives and how their use affects the short- and long-term outcomes of critically ill patients.22 Arroliga AC, Thompson BT, Ancukiewicz M, Gonzales JP, Guntupalli KK, Park PK, Wiedemann HP, Anzueto A; Acute Respiratory Distress Syndrome Network. Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2008;36(4):1083-8.,33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.) One of the key evidence-based concepts that emerged from observational studies and randomized controlled trials was a protocolized light sedation approach, which was included in recent guidelines.33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. Light sedation is considered the ideal target for most mechanically ventilated patients, where a “calm, comfortable and collaborative” state can ensure synchronous ventilation with minimal pain and anxiety, coupled with cognitive preservation. Potential patient-centered benefits of light sedation also include the possibility of active cognitive and motor stimulation (including early mobilization interventions) as well as improved interaction with the health care team and family members.44 Vincent JL, Shehabi Y, Walsh TS, Pandharipande PP, Ball JA, Spronk P, et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med. 2016;42(6):962-71.

What is the evidence behind light sedation?

Strong evidence demonstrates that oversedation is associated with worse clinical outcomes, and most recently, special attention has been given to the intensity of sedation in the early phase of MV. Studies demonstrate that allowing deep sedation even in the first 48 hours of MV can be detrimental. In a prospective multicenter longitudinal study on sedation practices comprising patients under MV for a period of 24 hours or more, Shehabi et al. demonstrated that early deep sedation was independently associated with longer time to extubation, hospital death and 180-day mortality.55 Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724-31. Similarly, an observational prospective multicenter study including 322 patients from 45 Brazilian ICUs showed that deep sedation within the first 48 hours of MV was independently associated with a 2-fold increase in hospital mortality.66 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. As “light sedation” uses fewer drugs and reduces overall resource use, it can be considered a cost-effective intervention in the ICU. Additionally, deep sedation is associated with worse functional and cognitive outcomes, as it decreases the possibility of early mobilization and significantly increases the risk of delirium.77 Shehabi Y, Bellomo R, Kadiman S, Ti LK, Howe B, Reade MC, Khoo TM, Alias A, Wong YL, Mukhopadhyay A, McArthur C, Seppelt I, Webb SA, Green M, Bailey MJ; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: a multinational prospective longitudinal cohort study. Crit Care Med. 2018;46(6):850-9.

Having a deeply sedated, immobilized patient transition to an awake and cooperative patient is an essential part of best practices in the ICU. However, it is not without its challenges. The ICU team must assure adequate control of potential distress and reduction of adverse outcomes using a multidisciplinary approach. Monitoring for pain and agitation is essential not only to the patients’ well-being but also for safety reasons, as an agitated patient may inadvertently remove intravascular devices or the endotracheal tube. Studies using light sedation have found that patients who are more awake and aware can contribution to their pain evaluations through reliable self-report, delirium assessments and early rehabilitation.33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.,44 Vincent JL, Shehabi Y, Walsh TS, Pandharipande PP, Ball JA, Spronk P, et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med. 2016;42(6):962-71. Light sedation was also associated with reduced ICU length of stay and shorter duration of MV with no increases in anxiety and depression88 Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, et al. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009;37(9):2527-34.. In studies where long-term follow-ups were reported, there was no sign of increased negative neuropsychological outcomes.99 Kress JP, Gehlbach B, Lacy M, Pliskin N, Pohlman AS, Hall JB. The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med. 2003;168(12):1457-61.

Who should receive light sedation in the intensive care unit?

The 2018 Pain, Agitation/Sedation, Delirium, Immobility and Sleep Disruption (PADIS) guidelines suggested a protocol-based, stepwise assessment for pain control and sedation management in critically ill adults.33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873. Clearly, the emphasis should not be on sedation but rather on multidisciplinary approaches to monitor, prevent and promptly treat pain and agitation while ensuring participation by an awake and aware patient. Light sedation was recommended for most patients to reduce anxiety and stress, to control symptoms of hyperactive delirium, and to facilitate invasive procedures and MV.33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.,1010 Olsen HT, Nedergaard HK, Strøm T, Oxlund J, Wian KA, Ytrebø LM, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med. 2020;382(12):1103-11. Additionally, the early comfort using analgesia, minimal sedatives and maximal human care (eCASH)44 Vincent JL, Shehabi Y, Walsh TS, Pandharipande PP, Ball JA, Spronk P, et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med. 2016;42(6):962-71. and the ABCDF-R bundle (R = respiratory-drive-control)1111 Devlin JW, O'Neal HR Jr, Thomas C, Barnes Daly MA, Stollings JL, Janz DR, et al. Strategies to optimize ICU liberation (A to F) Bundle performance in critically ill adults with coronavirus disease 2019. Crit Care Explor. 2020;2(6):e0139.,1212 Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, Aldrich JM, Barr J, et al. Caring for critically ill patients with the ABCDEF Bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2019;47(1):3-14.) guidelines emphasize the use of analgesia first with minimal sedation, communication aids, noise reduction to facilitate good sleep, early mobilization, delirium monitoring and family involvement as strategies to promote patient-centered care and comfort in the ICU.

Despite no universal definition of light sedation, guidelines considered a Richmond Agitation Sedation Scale (RASS) score of between +1 (slightly restless) and -2 (awake with eye contact to voice) or a Riker Sedation-Agitation Scale (SAS) score of between 4 (calm and cooperative) and 3 (difficult to rouse and obey simple commands) adequate for most patients.33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.,1010 Olsen HT, Nedergaard HK, Strøm T, Oxlund J, Wian KA, Ytrebø LM, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med. 2020;382(12):1103-11. Strategies to achieve light sedation such as daily interrupted sedation, targeted sedation or even no sedation can be used without a clear superiority of one over the other.1010 Olsen HT, Nedergaard HK, Strøm T, Oxlund J, Wian KA, Ytrebø LM, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med. 2020;382(12):1103-11.,1313 Hughes CG, Girard TD, Pandharipande PP. Daily sedation interruption versus targeted light sedation strategies in ICU patients. Crit Care Med. 2013;41(9 Suppl 1):S39-45.) A preference for the use of fast-acting sedative agents may allow dose titration and adjustment to the target level of consciousness.1414 Devlin JW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids. Crit Care Clin. 2009;25(3):431-49, vii.

Propofol or dexmedetomidine is recommended over benzodiazepines in patients requiring continuous sedation to achieve early33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.,55 Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724-31.,1515 Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506-17.) and continuous light sedation33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.,1616 Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151-60.) and to minimize the risk of delirium.1515 Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506-17. In sepsis patients, propofol and dexmedetomidine have been shown to be comparable in terms of clinical outcomes when light sedation was targeted.1717 Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, Jackson JC, Hoskins AS, Pun BT, Orun OM, Raman R, Stollings JL, Kiehl AL, Duprey MS, Bui LN, O'Neal HR Jr, Snyder A, Gropper MA, Guntupalli KK, Stashenko GJ, Patel MB, Brummel NE, Girard TD, Dittus RS, Bernard GR, Ely EW, Pandharipande PP; MENDS2 Study Investigators. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. 2021;384(15):1424-36. Opioids remain a mainstay for pain management in the ICU,33 Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.,1818 Wheeler KE, Grilli R, Centofanti JE, Martin J, Gelinas C, Szumita PM, et al. Adjuvant analgesic use in the critically ill: a systematic review and meta-analysis. Crit Care Explor. 2020;2(7):e0157. but the use of adjuvant analgesic therapy, such as acetaminophen, clonidine, dexmedetomidine, gabapentin, ketamine, pregabalin, and tramadol, promotes a reduction in pain scores as well as a reduction in opioid consumption, as demonstrated in a recent meta-analysis.1818 Wheeler KE, Grilli R, Centofanti JE, Martin J, Gelinas C, Szumita PM, et al. Adjuvant analgesic use in the critically ill: a systematic review and meta-analysis. Crit Care Explor. 2020;2(7):e0157. Only a minority of the patients admitted to the ICU have a clear indication for continuous deep sedation: patients with severe respiratory failure, status epilepticus, intracranial hypertension and the need for neuromuscular blockade.1919 Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016;44(11):2079-103.) Patients with these conditions may be underrepresented in studies on analgesia and sedation because they are frequently excluded.1010 Olsen HT, Nedergaard HK, Strøm T, Oxlund J, Wian KA, Ytrebø LM, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med. 2020;382(12):1103-11.,1919 Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016;44(11):2079-103.) However, even when deep sedation is needed, it should be considered a transitory strategy, and the use of combinations of sedatives may be used to minimize the use of benzodiazepines.1919 Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016;44(11):2079-103.

A schematic approach to analgesia and sedation is suggested in figure 1.

Figure 1
Schematic approach to analgesia and sedation.

CONCLUSION

In conclusion, recent studies demonstrate that the use of light sedation is feasible and safe in most mechanically ventilated patients in the intensive care unit. The shift from a deeply sedated patient to a calm, comfortable and collaborative patient is associated with reduced intensive care unit stay, duration of mechanical ventilation and delirium as well as improved survival rates. The use of light sedation is a cost-effective, evidence-based strategy that should be considered the standard of care in the intensive care unit.

References

  • 1
    Puntillo KA, Max A, Timsit JF, Vignoud L, Chanques G, Robleda G, et al. Determinants of procedural pain intensity in the intensive care unit. The Europain(r) study. Am J Respir Crit Care Med. 2014;189(1):39-47.
  • 2
    Arroliga AC, Thompson BT, Ancukiewicz M, Gonzales JP, Guntupalli KK, Park PK, Wiedemann HP, Anzueto A; Acute Respiratory Distress Syndrome Network. Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2008;36(4):1083-8.
  • 3
    Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobilit y, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.
  • 4
    Vincent JL, Shehabi Y, Walsh TS, Pandharipande PP, Ball JA, Spronk P, et al. Comfort and patient-centred care without excessive sedation: the eCASH concept. Intensive Care Med. 2016;42(6):962-71.
  • 5
    Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012;186(8):724-31.
  • 6
    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.
  • 7
    Shehabi Y, Bellomo R, Kadiman S, Ti LK, Howe B, Reade MC, Khoo TM, Alias A, Wong YL, Mukhopadhyay A, McArthur C, Seppelt I, Webb SA, Green M, Bailey MJ; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: a multinational prospective longitudinal cohort study. Crit Care Med. 2018;46(6):850-9.
  • 8
    Treggiari MM, Romand JA, Yanez ND, Deem SA, Goldberg J, Hudson L, et al. Randomized trial of light versus deep sedation on mental health after critical illness. Crit Care Med. 2009;37(9):2527-34.
  • 9
    Kress JP, Gehlbach B, Lacy M, Pliskin N, Pohlman AS, Hall JB. The long-term psychological effects of daily sedative interruption on critically ill patients. Am J Respir Crit Care Med. 2003;168(12):1457-61.
  • 10
    Olsen HT, Nedergaard HK, Strøm T, Oxlund J, Wian KA, Ytrebø LM, et al. Nonsedation or light sedation in critically ill, mechanically ventilated patients. N Engl J Med. 2020;382(12):1103-11.
  • 11
    Devlin JW, O'Neal HR Jr, Thomas C, Barnes Daly MA, Stollings JL, Janz DR, et al. Strategies to optimize ICU liberation (A to F) Bundle performance in critically ill adults with coronavirus disease 2019. Crit Care Explor. 2020;2(6):e0139.
  • 12
    Pun BT, Balas MC, Barnes-Daly MA, Thompson JL, Aldrich JM, Barr J, et al. Caring for critically ill patients with the ABCDEF Bundle: results of the ICU liberation collaborative in over 15,000 adults. Crit Care Med. 2019;47(1):3-14.
  • 13
    Hughes CG, Girard TD, Pandharipande PP. Daily sedation interruption versus targeted light sedation strategies in ICU patients. Crit Care Med. 2013;41(9 Suppl 1):S39-45.
  • 14
    Devlin JW, Roberts RJ. Pharmacology of commonly used analgesics and sedatives in the ICU: benzodiazepines, propofol, and opioids. Crit Care Clin. 2009;25(3):431-49, vii.
  • 15
    Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early sedation with dexmedetomidine in critically ill patients. N Engl J Med. 2019;380(26):2506-17.
  • 16
    Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012;307(11):1151-60.
  • 17
    Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, Jackson JC, Hoskins AS, Pun BT, Orun OM, Raman R, Stollings JL, Kiehl AL, Duprey MS, Bui LN, O'Neal HR Jr, Snyder A, Gropper MA, Guntupalli KK, Stashenko GJ, Patel MB, Brummel NE, Girard TD, Dittus RS, Bernard GR, Ely EW, Pandharipande PP; MENDS2 Study Investigators. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. 2021;384(15):1424-36.
  • 18
    Wheeler KE, Grilli R, Centofanti JE, Martin J, Gelinas C, Szumita PM, et al. Adjuvant analgesic use in the critically ill: a systematic review and meta-analysis. Crit Care Explor. 2020;2(7):e0157.
  • 19
    Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, et al. Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient. Crit Care Med. 2016;44(11):2079-103.

Publication Dates

  • Publication in this collection
    08 Nov 2021
  • Date of issue
    2021

History

  • Received
    23 Apr 2021
  • Accepted
    23 May 2021
Associação de Medicina Intensiva Brasileira - AMIB Rua Arminda, 93 - Vila Olímpia, CEP 04545-100 - São Paulo - SP - Brasil, Tel.: (11) 5089-2642 - São Paulo - SP - Brazil
E-mail: rbti.artigos@amib.com.br