Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality

A multinational prospective longitudinal cohort study

Yahya Shehabi, Rinaldo Bellomo, Suhaini Kadiman, Lian Kah Ti, Belinda Howe, Michael C. Reade, Tien Meng Khoo, Anita Alias, Yu Lin Wong, Amartya Mukhopadhyay, Colin McArthur, I. Seppelt, Steven A. Webb, Maja Green, Michael J. Bailey, for the Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Design: Harmonized data from prospective multicenter international longitudinal cohort studies Setting: Diverse mix of ICUs. Patients: Critically ill patients expected to be ventilated for longer than 24 hours. Interventions: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Measurements and Main Results: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (sd) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Conclusions: Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

Original languageEnglish
Pages (from-to)850-859
Number of pages10
JournalCritical Care Medicine
Volume46
Issue number6
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Critically ill
  • Delirium
  • Mechanical ventilation
  • Mobilization
  • Mortality
  • Sedation intensity

Cite this

Shehabi, Y., Bellomo, R., Kadiman, S., Ti, L. K., Howe, B., Reade, M. C., ... for the Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group (2018). Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: A multinational prospective longitudinal cohort study. Critical Care Medicine, 46(6), 850-859. https://doi.org/10.1097/CCM.0000000000003071
Shehabi, Yahya ; Bellomo, Rinaldo ; Kadiman, Suhaini ; Ti, Lian Kah ; Howe, Belinda ; Reade, Michael C. ; Khoo, Tien Meng ; Alias, Anita ; Wong, Yu Lin ; Mukhopadhyay, Amartya ; McArthur, Colin ; Seppelt, I. ; Webb, Steven A. ; Green, Maja ; Bailey, Michael J. ; for the 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. In: Critical Care Medicine. 2018 ; Vol. 46, No. 6. pp. 850-859.
@article{4192749f2677454cb1504186e1ae64c6,
title = "Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: A multinational prospective longitudinal cohort study",
abstract = "Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Design: Harmonized data from prospective multicenter international longitudinal cohort studies Setting: Diverse mix of ICUs. Patients: Critically ill patients expected to be ventilated for longer than 24 hours. Interventions: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Measurements and Main Results: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (sd) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3{\%} (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8{\%}) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95{\%} CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95{\%} CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95{\%} CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95{\%} CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Conclusions: Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.",
keywords = "Critically ill, Delirium, Mechanical ventilation, Mobilization, Mortality, Sedation intensity",
author = "Yahya Shehabi and Rinaldo Bellomo and Suhaini Kadiman and Ti, {Lian Kah} and Belinda Howe and Reade, {Michael C.} and Khoo, {Tien Meng} and Anita Alias and Wong, {Yu Lin} and Amartya Mukhopadhyay and Colin McArthur and I. Seppelt and Webb, {Steven A.} and Maja Green and Bailey, {Michael J.} and {for the Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group} and E. Ibrom and C. Maher and C. Mashonganyika and H. McKee and V. Bennett and Cooper, {D. J.} and S. Vallance and G. Eastwood and L. Peck and M. Reade and H. Young and S. Eliott and I. Mercer and J. Sidhu and A. Whitfield and G. Ding and P. Hatfield and K. Smith and T. Coles and J. Dennett and T. Summers and R. Anderson and E. Jones and D. Milliss and H. Wong and J. Botha and S. Allsop and M. Kanhere and J. Wood and C. Hogan and J. Tai and T. Williams and A. Buckley and P. Garrett and S. McDonald and C. Cuzner and I. Seppelt and L. Weisbrodt and F. Bass and P. Edhouse and M. Sana and J. Chamberlain and A. Bicknell and B. Roberts and E. Casey and A. Cheng and D. Inskip and J. Myburgh and J. Holmes and J. Santamaria and R. Smith and P. Nair and C. Reynolds and B. Johnson and M. Sterba and Wong, {K. K.} and Suresh Venugopal and Vineya Rai and Mohd Shahnaz and Vimala Ramoo and Smitha Jose and Ozlem Ozturk and Ramlee, {S. N.Zuraida} and Foon, {Bong Siu} and Rohana Amran and Narula, {R. K.Anusha} and {Md Ramly}, {Erin Shazrin} and Hapiz, {Khalidah Abdul} and Lim I-Liang and Morad, {Mohamad Hafiz Che} and Ali, {Mohd Nazri} and Raihan, {H. Noor} and Azizum, {Sister I.} and Y. Suzana and H. Haryati and Zawati, {S. Salmi} and Ismeev, {J. Nur} and Zulkarnain, {Mohd Ashraf} and Mahamarowi Omar and Omar, {Siti Aisah} and Ismail, {Sister Rokian} and Norhamilah Hassan and Zanariah Zakaria and Sanah Mohtar and Marina Ahmad and Winnie Suai and {Ai Li}, Wong and Lan, {Jong Siaw} and Rohayah, {S. Siti} and Fitriah Mahadir and Lian, {Teoh Shook} and Zain, {Maryam Md} and Noorasmah Ahmad and K. Mahazir and Bakar, {A'ishah Abu} and Nan, {Ho Wing} and {Tan Ai Ping}, Sister and Ngan, {Sister Chin Lai} and Har, {Lim Chiew} and Jahizah Hassan and J. Brown and E. Gilders and R. Parke and C. McArthur and L. Newby and C. Simmonds and S. Henderson and J. Mehrtens and T. Browne and D. Cubis and J. Goodson and S. Nelson and D. MacKle and S. Pecher and L. Ti and D. Lim and A. Mukhopadhyay and Y. Wong and B. Ho and N. Chia and N. Yi and G. Kalyanasundaram",
year = "2018",
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doi = "10.1097/CCM.0000000000003071",
language = "English",
volume = "46",
pages = "850--859",
journal = "Critical Care Medicine",
issn = "0090-3493",
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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 & for the Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group 2018, 'Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality: A multinational prospective longitudinal cohort study', Critical Care Medicine, vol. 46, no. 6, pp. 850-859. https://doi.org/10.1097/CCM.0000000000003071

Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality : A multinational prospective longitudinal cohort study. / Shehabi, Yahya; Bellomo, Rinaldo; Kadiman, Suhaini; Ti, Lian Kah; Howe, Belinda; Reade, Michael C.; Khoo, Tien Meng; Alias, Anita; Wong, Yu Lin; Mukhopadhyay, Amartya; McArthur, Colin; Seppelt, I.; Webb, Steven A.; Green, Maja; Bailey, Michael J.; for the Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group.

In: Critical Care Medicine, Vol. 46, No. 6, 01.01.2018, p. 850-859.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Sedation intensity in the first 48 hours of mechanical ventilation and 180-day mortality

T2 - A multinational prospective longitudinal cohort study

AU - Shehabi, Yahya

AU - Bellomo, Rinaldo

AU - Kadiman, Suhaini

AU - Ti, Lian Kah

AU - Howe, Belinda

AU - Reade, Michael C.

AU - Khoo, Tien Meng

AU - Alias, Anita

AU - Wong, Yu Lin

AU - Mukhopadhyay, Amartya

AU - McArthur, Colin

AU - Seppelt, I.

AU - Webb, Steven A.

AU - Green, Maja

AU - Bailey, Michael J.

AU - for the Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group

AU - Ibrom, E.

AU - Maher, C.

AU - Mashonganyika, C.

AU - McKee, H.

AU - Bennett, V.

AU - Cooper, D. J.

AU - Vallance, S.

AU - Eastwood, G.

AU - Peck, L.

AU - Reade, M.

AU - Young, H.

AU - Eliott, S.

AU - Mercer, I.

AU - Sidhu, J.

AU - Whitfield, A.

AU - Ding, G.

AU - Hatfield, P.

AU - Smith, K.

AU - Coles, T.

AU - Dennett, J.

AU - Summers, T.

AU - Anderson, R.

AU - Jones, E.

AU - Milliss, D.

AU - Wong, H.

AU - Botha, J.

AU - Allsop, S.

AU - Kanhere, M.

AU - Wood, J.

AU - Hogan, C.

AU - Tai, J.

AU - Williams, T.

AU - Buckley, A.

AU - Garrett, P.

AU - McDonald, S.

AU - Cuzner, C.

AU - Seppelt, I.

AU - Weisbrodt, L.

AU - Bass, F.

AU - Edhouse, P.

AU - Sana, M.

AU - Chamberlain, J.

AU - Bicknell, A.

AU - Roberts, B.

AU - Casey, E.

AU - Cheng, A.

AU - Inskip, D.

AU - Myburgh, J.

AU - Holmes, J.

AU - Santamaria, J.

AU - Smith, R.

AU - Nair, P.

AU - Reynolds, C.

AU - Johnson, B.

AU - Sterba, M.

AU - Wong, K. K.

AU - Venugopal, Suresh

AU - Rai, Vineya

AU - Shahnaz, Mohd

AU - Ramoo, Vimala

AU - Jose, Smitha

AU - Ozturk, Ozlem

AU - Ramlee, S. N.Zuraida

AU - Foon, Bong Siu

AU - Amran, Rohana

AU - Narula, R. K.Anusha

AU - Md Ramly, Erin Shazrin

AU - Hapiz, Khalidah Abdul

AU - I-Liang, Lim

AU - Morad, Mohamad Hafiz Che

AU - Ali, Mohd Nazri

AU - Raihan, H. Noor

AU - Azizum, Sister I.

AU - Suzana, Y.

AU - Haryati, H.

AU - Zawati, S. Salmi

AU - Ismeev, J. Nur

AU - Zulkarnain, Mohd Ashraf

AU - Omar, Mahamarowi

AU - Omar, Siti Aisah

AU - Ismail, Sister Rokian

AU - Hassan, Norhamilah

AU - Zakaria, Zanariah

AU - Mohtar, Sanah

AU - Ahmad, Marina

AU - Suai, Winnie

AU - Ai Li, Wong

AU - Lan, Jong Siaw

AU - Rohayah, S. Siti

AU - Mahadir, Fitriah

AU - Lian, Teoh Shook

AU - Zain, Maryam Md

AU - Ahmad, Noorasmah

AU - Mahazir, K.

AU - Bakar, A'ishah Abu

AU - Nan, Ho Wing

AU - Tan Ai Ping, Sister

AU - Ngan, Sister Chin Lai

AU - Har, Lim Chiew

AU - Hassan, Jahizah

AU - Brown, J.

AU - Gilders, E.

AU - Parke, R.

AU - McArthur, C.

AU - Newby, L.

AU - Simmonds, C.

AU - Henderson, S.

AU - Mehrtens, J.

AU - Browne, T.

AU - Cubis, D.

AU - Goodson, J.

AU - Nelson, S.

AU - MacKle, D.

AU - Pecher, S.

AU - Ti, L.

AU - Lim, D.

AU - Mukhopadhyay, A.

AU - Wong, Y.

AU - Ho, B.

AU - Chia, N.

AU - Yi, N.

AU - Kalyanasundaram, G.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Design: Harmonized data from prospective multicenter international longitudinal cohort studies Setting: Diverse mix of ICUs. Patients: Critically ill patients expected to be ventilated for longer than 24 hours. Interventions: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Measurements and Main Results: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (sd) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Conclusions: Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

AB - Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Design: Harmonized data from prospective multicenter international longitudinal cohort studies Setting: Diverse mix of ICUs. Patients: Critically ill patients expected to be ventilated for longer than 24 hours. Interventions: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Measurements and Main Results: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (sd) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. Conclusions: Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

KW - Critically ill

KW - Delirium

KW - Mechanical ventilation

KW - Mobilization

KW - Mortality

KW - Sedation intensity

UR - http://www.scopus.com/inward/record.url?scp=85049692415&partnerID=8YFLogxK

U2 - 10.1097/CCM.0000000000003071

DO - 10.1097/CCM.0000000000003071

M3 - Article

VL - 46

SP - 850

EP - 859

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 6

ER -