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1 Supplementary Online Content Gershengorn HB, Scales DC, Kramer A, Wunsch H. Association between overnight extubations and outcomes in the intensive care unit. JAMA Intern Med. Published online September 6, doi: /jamainternmed efigure 1. CONSORT Diagram efigure 2. Proportion of Overnight Extubations by Year of ICU Admission efigure 3. Unadjusted Time of Day of Extubations Stratified by Duration of Mechanical Ventilation efigure 4. Unadjusted Time of Day of Extubations Stratified by Location Before ICU Admission, Admission Type, and ICU Type efigure 5. Time to Intensive Care Unit/Hospital Discharge for Propensity-Matched Pairs Accounting for the Competing Risk of Death efigure 6. Distribution of Time of Day of Extubations in APACHE Outcomes Cohort efigure 7. Odds of Reintubation and Mortality Associated With Overnight Extubation for Propensity-Matched Pairs for Sensitivity Analyses Stratified by Patient Subgroup etable 1. Characteristics of Cohort Intensive Care Units etable 2. Multivariate Adjusted Risk Factors Associated With Overnight Extubation etable 3. Characteristics of Cohort Patients Stratified by Completeness of Covariate Data etable 4. Characteristics of Cohort Patients Stratified by Duration of Mechanical Ventilation etable 5. Baseline Characteristics of Propensity-Matched Pairs etable 6. Baseline Characteristics and Outcomes of Propensity-Matched Pairs From APACHE Outcomes Cohort etable 7. Length of Stay for Propensity-Matched Pairs From Sensitivity Analyses Stratified by Patient Subgroup This supplementary material has been provided by the authors to give readers additional information about their work.

2 efigure 1. CONSORT Diagram ICU: intensive care unit; MPM 0 -III: Mortality Probability Model 0 -III; MV: mechanical ventilation a Patients after cardiac surgery or organ transplantation and those with acute myocardial infarction were excluded from derivation of Mortality Probability Model 0 -III and, thus, this severity of illness score does not apply and was not calculated for them

3 efigure 2. Proportion of Overnight Extubations by Year of ICU Admission a 25% 20% Percent of Extubations 15% 10% 5% 0% ICU Admission Year a Bars represent 95% confidence intervals of the estimate; p<0.001

4 efigure 3. Unadjusted Time of Day of Extubations Stratified by Duration of Mechanical Ventilation. 16% 14% 12% 10% 8% <0.5 <12 hours 0.5 <1 12 h <1 day 1 <2 1 <2 days 2 <7 2 <7 days 7+ days Total 6% 4% 2% 0% Hour of Day

5 efigure 4. Unadjusted Time of Day of Extubations Stratified by Location Before ICU Admission, Admission Type, and ICU Type A. Location Prior to ICU Admission 14% 12% 10% 8% 6% ER OR/PACU ward SDUtele other Total 4% 2% 0% Hour of Day B. Admission Type 15% 10% surgical medical total 5% 0% Hour of Day C. ICU Type 16% 14% 12% 10% 8% 6% 4% 2% 0% medical I surgical med surg other Total Hour of Day ER: emergency room; ICU: intensive care unit; OR/PACU: operating room/postanesthesia care unit; SDUtele: stepdown unit or telemetry unit

6 efigure 5. Time to Intensive Care Unit/Hospital Discharge for Propensity-Matched Pairs Accounting for the Competing Risk of Death ICU: intensive care unit; IQR: interquartile range; LOS: length of stay; MV: mechanical ventilation

7 efigure 6. Distribution of Time of Day of Extubations in APACHE Outcomes Cohort a 12% Overnight Daytime Overnight 10% Percent of Extubations 8% 6% 4% 2% 0% Hour of day a 82% of extubations occur during the daytime

8 efigure 7. Odds of Reintubation and Mortality Associated With Overnight Extubation for Propensity-Matched Pairs for Sensitivity Analyses Stratified by Patient Subgroup A. Patients Mechanically Ventilated < 12 Hours. a B. Patients Mechanically Ventilated 12 Hours. b ICU: intensive care unit; Neuro: neurological

9 a Project IMPACT overnight =0:00a-4:59a: 1256 out of 1254 (>99%); hospital survivors: 4135 out of 4142 (>99%); survivors 24hrs post-extubation: 4257 out of 4265 (>99%); patients remaining extubated >1hr: 4449 out of 4454 (>99%); APACHE Outcomes full cohort: 2575 out of 2710 overnight extubations matched (95%); overnight =0:00a-4:59a: 763 out of 771 (99%); medical patients: 1007 out of 1011 (>99%); elective surgical patients: 1180 out of 1534 (77%); emergent surgical patients: 163 out of 185 (88%); Medical ICU: 330 out of 349 (95%%); Surgical ICU: 919 out of 1016 (90%); Medical-Surgical ICU: 1079 out of 1199 (90%); Neurological ICU: 115 out of 139 (83%) hospital survivors: 2213 out of 2398 (92%); survivors 24hrs postextubation: 2310 out of 2489 (93%); patients remaining extubated >1hr: 2551 out of 2689 (95%) b Project IMPACT overnight =0:00a-4:59a: 1256 out of 1256 (100%); hospital survivors: 4834 out of 4835 (>99%); survivors 24hrs post-extubation: 5107 out of 5109 (>99%); patients remaining extubated >1hr: 5549 out of 5551 (>99%); APACHE Outcomes full cohort: 2963 out of 2965 overnight extubations matched (>99%); overnight =0:00a-4:59a: 775 out of 775 (100%); medical patients: 2225 out of 2226 (>99%); elective surgical patients: 459 out of 505 (91%); emergent surgical patients: 234 out of 234 (100%); Medical ICU: 787 out of 788 (>99%%); Surgical ICU: 583 out of 583 (100%); Medical-Surgical ICU: 1380 out of 1382 (>99%); Neurological ICU: 190 out of 190 (100%); hospital survivors: 1989 out of 1990 (>99%); survivors 24hrs postextubation: 2185 out of 2186 (>99%); patients remaining extubated >1hr: 2892 out of 2893 (>99%)

10 etable 1. Characteristics of Cohort Intensive Care Units N (%) a # of ICUs 165 (100) ICU type Medical ICU 30 (18.2) Surgical ICU 40 (24.2) Med-Surg ICU 84 (50.9) Other 7 (4.2) # of ICU beds (22.4) (7.3) (7.3) (13.9) (8.5) (15.8) (14.5) (6.7) 6 2 (1.2) ICU Model closed or mandatory CC 43 (26.1) consult Onsite Night Coverage Intensivist 44 (26.7) Other clinician 103 (62.4) None 1 (0.6) Nurse-to-Patient Ratio 1:1-1:2 157 (95.2) 1:3-1:4 7 (4.3) United States region New England 15 (9.2) Mid-Atlantic 24 (14.6) South Atlantic 25 (15.2) East-North-Central 41 (25.0) East-South-Central 5 (3.1) West-North-Central 21 (12.8) West-South-Central 17 (10.4) Mountain 6 (3.7) West 10 (6.1) Teaching hospital 38 (23.0) CC: critical care; ICU: intensive care unit; Med-Surg: medical-surgical a Data were missing for: ICU type 4 ICUs; # of ICU beds 4 ICUs; ICU model 3 ICUs; Onsite Night Coverage 17 ICUs; Nurse-to-Patient Ratio 1 ICU; U.S. region 1 ICU

11 etable 2. Multivariate Adjusted Risk Factors Associated With Overnight Extubation a Risk Factor AOR (95% CI) P Value ICU admission year (0.88,1.07) (0.85,1.04) (0.78,0.96) (0.77,0.96) (0.71,0.88) < (0.69,0.87) < (0.57,0.74) < (0.48,0.96).029 Age Cubic spline term (0.99,1.00).16 Cubic spline term (0.98,1.00).29 Cubic spline term (0.98,1.09).25 Race White 1 Black 0.93 (0.87,1.00).06 Other 0.99 (0.91,1.09).90 Female 0.97 (0.93,1.02).19 Admission type Elective surgical 1 Emergent surgical 0.78 (0.72,0.84) <.001 Medical 0.79 (0.71,0.89) <.001 Insurance Private insurance 1 Medicare 1.00 (0.93,1.07).90 Medicaid 1.00 (0.92,1.09).92 Self pay 0.91 (0.84,0.99).021 Other 0.94 (0.83,1.06).32 Location prior to ICU Emergency room 1 OR/PACU 1.01 (0.91,1.12).89 Ward 1.02 (0.92,1.12).75 SDU/telemetry 0.98 (0.87,1.11).80 Other 1.04 (0.95,1.13).39 Diagnostic Group Respiratory/thoracic 1 Cardiovascular 1.18 (1.10,1.27) <.001 Sepsis 1.15 (1.04,1.27).007 Trauma 1.15 (1.06,1.25).001 Neurologic 1.21 (1.12,1.31) <.001 Metabolic/renal 1.01 (0.91,1.12).82

12 Gastrointestinal 1.14 (1.05,1.24).001 Mortality Probability Model 0 -III Cubic spline term (1.12,30.86).036 Cubic spline term (0.00,395.43).14 Cubic spline term E+12 (8.55E-5, 7.54E+29).14 Comorbidities GI system 1.10 (0.97,1.25).15 CV system 1.16 (1.03,1.30).014 Respiratory System 0.87 (0.79,0.96).007 Renal System Creatinine> (0.90,1.15).74 Dialysis 1.03 (0.88,1.20).70 Immunocompromised AIDS 1.16 (0.86,1.56).32 Steroids 0.85 (0.68,1.06).14 Non-steroid meds (0.91,1.29).36 Leuk/Lymph/Myel 1.11 (0.81,1.54).51 Other 0.81 (0.55,1.19).29 Malignancy Chemo/XRT (1 yr) 1.17 (1.00,1.38).06 Chemo/XRT (HD/lymph anytime) 0.87 (0.57,1.34).54 Hematologic (5 yrs) 0.98 (0.68,1.42).92 Lymphoma (5 yrs) 1.19 (0.84,1.69).33 Solid organ (5 yrs) 0.96 (0.85,1.07).43 Metastases (5 yrs) 1.02 (0.90,1.17).74 MV on ICU admission 0.89 (0.83,0.95).001 MV duration <12 hours 1 12 hours - < 1 day 0.20 (0.19,0.21) < <2 days 0.26 (0.24,0.28) < <7 days 0.22 (0.21,0.24) < days 0.24 (0.22,0.26) <.001 ICU type Medical ICU 1 Surgical ICU 1.34 (1.11,1.61).002 Med-Surg ICU 1.25 (1.05,1.49).013 Other/unknown 1.70 (1.10,2.63).018 # of ICU beds (0.73,1.12) (0.64,0.84) < (0.68,0.99) (0.69,1.01) (0.71,1.00).045

13 (0.75,1.09) (0.56,0.99) (0.99,12.45).051 ICU Model closed/mandatory CC consult 1 open/possible CC consult 0.91 (0.79,1.03).145 Onsite Night Coverage Intensivist 1 Other clinician 0.81 (0.72,0.91).001 None 0.75 (0.31,1.79).517 Nurse-to-Patient Ratio 1:1-1:2 1 1:3-1: (0.63,1.14).277 United States region New England 1 Mid-Atlantic 1.14 (0.90,1.45).29 South Atlantic 1.13 (0.90,1.41).289 East-North-Central 1.27 (1.03,1.58).028 East-South-Central 1.58 (1.13,2.21).008 West-North-Central 1.11 (0.86,1.44).43 West-South-Central 1.46 (1.12,1.91).005 Mountain 1.37 (0.99,1.90).061 West 1.37 (1.01,1.87).045 Teaching hospital 1.26 (1.07,1.49).006 AIDS: autoimmune deficiency syndrome; CC: critical care; Chemo/XRT: chemotherapy and radiation therapy; CV: cardiovascular; GI: gastrointestinal; HD/lymph: Hodgkin s Disease and lymphoma; ICU: intensive care unit; IQR: interquartile range; Leuk/Lymph/ Myel: leukemia, lymphoma, myeloma; Med-Surg: Medical-Surgical; MV: mechanical ventilation; OR/PACU: operating room/post-anesthesia care unit; sd: standard deviation; SDU: stepdown unit a Model based on 73,164 (74.8% of full cohort) patients with all covariate data available

14 etable 3. Characteristics of Cohort Patients Stratified by Completeness of Covariate Data Characteristic a Full Cohort All Covariates Available At Least One Covariate Not Available Total patients, N(%) 97,844 (100.0) 73,164 (74.8) 24,680 (25.2) P Value b Age (years), mean±sd 58.3± ± ±14.5 <.001 Race <.001 White Black Other Female <.001 Admission type <.001 Elective surgical Emergent surgical Medical Insurance <.001 Private insurance Medicare Medicaid Self pay Other Location prior to ICU <.001 Emergency room OR/PACU Ward SDU/telemetry Other Diagnostic Group <.001 Respiratory/thoracic Cardiovascular Sepsis Trauma Neurologic Metabolic/renal Gastrointestinal Mortality Probability Model %±16.5% 17.1%±16.5% 15.4%±16.3% <.001 III, mean±sd Comorbidities GI system <.001 CV system <.001 Respiratory System <.001 Renal System

15 Creatinine> <.001 Dialysis <.001 Immunocompromised AIDS <.001 Steroids <.001 Non-steroid meds <.001 Leuk/Lymph/Myel <.001 Other Malignancy Chemo/XRT (1 yr) <.001 Chemo/XRT (HD/lymph anytime) Hematologic (5 yrs) Lymphoma (5 yrs) Solid organ (5 yrs) <.001 Metastases (5 yrs) <.001 MV on ICU admission <.001 Duration of MV (days), 3.0± ± ±3.4 <.001 mean±sd DNR on ICU discharge <.001 ICU admission year < ICU type <.001 Medical ICU Surgical ICU Med-Surg ICU Other United States region <.001 New England Mid-Atlantic South Atlantic East-North-Central East-South-Central West-North-Central West-South-Central Mountain West

16 # of ICU beds < ICU Model closed or <.001 mandatory CC consult Onsite Night Coverage <.001 Intensivist Other clinician None Nurse-to-Patient Ratio <.001 1:1-1: :3-1: Teaching Hospital AIDS: autoimmune deficiency syndrome; CC: critical care; Chemo/XRT: chemotherapy and radiation therapy; CV: cardiovascular; DNR: do-not-resuscitate; GI: gastrointestinal; HD/lymph: Hodgkin s Disease and lymphoma; ICU: intensive care unit; IQR: interquartile range; Leuk/Lymph/ Myel: leukemia, lymphoma, myeloma; Med-Surg: Medical-Surgical; MV: mechanical ventilation; OR/PACU: operating room/postanesthesia care unit; sd: standard deviation; SDU: stepdown unit a Data were missing for: race 1944 patients, gender 17 patients, insurance 1009 patients, location prior to ICU 7 patients; diagnostic group 1 patient; ICU type 2683 patients; # of ICU beds 2683 patients; ICU model 429 patients; onsite night coverage 5686 patients; nurse-to-patient ratio 290 patients; U.S. region 262 patients; and teaching hospital 268 patients; Mortality Probability Model 0 -III was not applicable to and, thus, not calculated for patients as they were post-cardiac or transplant surgery or admitted with an acute myocardial infarction b Comparison between patients with all covariates available and those with at least one covariate not available: t-test for continuous variables; Chi square for categorical variables

17 etable 4. Characteristics of Cohort Patients Stratified by Duration of Mechanical Ventilation Characteristic a MV<12 hours MV 12 hours P Value b Total patients, N(%) 26,679 (27.3) 71,165 (72.7) Age (years), mean±sd 58.1± ± Race White <.001 Black Other Female <.001 Admission type Elective surgical <.001 Emergent surgical Medical Insurance Private insurance <.001 Medicare Medicaid Self pay Other Location prior to ICU Emergency room <.001 OR/PACU Ward SDU/telemetry Other Diagnostic Group Respiratory/thoracic <.001 Cardiovascular Sepsis Trauma Neurologic Metabolic/renal Gastrointestinal Mortality Probability Model 0 -III, 13.4%±14.5% 18.0%±16.8% <.001 mean±sd Comorbidities GI system <.001 CV system <.001 Respiratory System <.001 Renal System Creatinine> <.001 Dialysis <.001

18 Immunocompromised AIDS <.001 Steroids <.001 Non-steroid meds <.001 Leuk/Lymph/Myel <.001 Other Malignancy Chemo/XRT (1 yr) <.001 Chemo/XRT (HD/lymph anytime) Hematologic (5 yrs) Lymphoma (5 yrs) <.001 Solid organ (5 yrs) <.001 Metastases (5 yrs) <.001 MV on ICU admission <.001 Duration of MV (days), mean±sd 0.3± ±5.4 <.001 DNR on ICU discharge ICU admission year < ICU type <.001 Medical ICU Surgical ICU Med-Surg ICU Other United States region <.001 New England Mid-Atlantic South Atlantic East-North-Central East-South-Central West-North-Central West-South-Central Mountain West # of ICU beds <

19 ICU Model closed or mandatory CC <.001 consult Onsite Night Coverage <.001 Intensivist Other clinician None Nurse-to-Patient Ratio <.001 1:1-1: :3-1: Teaching Hospital AIDS: autoimmune deficiency syndrome; CC: critical care; Chemo/XRT: chemotherapy and radiation therapy; CV: cardiovascular; DNR: do-not-resuscitate; GI: gastrointestinal; HD/lymph: Hodgkin s Disease and lymphoma; ICU: intensive care unit; IQR: interquartile range; Leuk/Lymph/ Myel: leukemia, lymphoma, myeloma; Med-Surg: Medical-Surgical; MV: mechanical ventilation; OR/PACU: operating room/postanesthesia care unit; sd: standard deviation; SDU: stepdown unit a Data were missing for: race 1944 patients, gender 17 patients, insurance 1009 patients, location prior to ICU 7 patients; diagnostic group 1 patient; ICU type 2683 patients; # of ICU beds 2683 patients; ICU model 429 patients; onsite night coverage 5686 patients; nurse-to-patient ratio 290 patients; U.S. region 262 patients; and teaching hospital 268 patients; Mortality Probability Model 0 -III was not applicable to and, thus, not calculated for patients as they were post-cardiac or transplant surgery or admitted with an acute myocardial infarction Indicates t-test for continuous variables; Chi square for categorical variables

20 etable 5. Baseline Characteristics of Propensity-Matched Pairs Patients with MV < 12 hours Daytime Overnight Extubation Extubation (7a-6p) (7p-6a) P Value a Patients with MV 12 hours Daytime Overnight Extubation Extubation (7a-6p) (7p-6a) P Value a # of Patients b Characteristics Age (years), mean±sd 55.3± ± ± ± Race White Black Other Female Admission type Elective surgical Emergent surgical Medical Insurance Private insurance Medicare Medicaid Self pay Other Location prior to ICU Emergency room OR/PACU Ward SDU/telemetry Other

21 Diagnostic Group Respiratory/thoracic Cardiovascular Sepsis Trauma Neurologic Metabolic/renal Gastrointestinal Mortality Probability Model 0 -III, 13.5% ±15.0% 13.3% ±14.6% % ±18.7% 18.8% ±18.4%.75 mean±sd Comorbidities GI system CV system Respiratory System Renal System Creatinine> Dialysis Immunocompromised AIDS Steroids Non-steroid meds Leuk/Lymph/Myel Other Malignancy Chemo/XRT (1 yr) Chemo/XRT (HD/lymph anytime) Hematologic (5 yrs) Lymphoma (5 yrs) > Solid organ (5 yrs) Metastases (5 yrs) MV on ICU admission

22 Duration of MV (days), mean±sd 0.2± ± ± ± DNR on ICU discharge, c % ICU admission year ICU type Medical ICU Surgical ICU Med-Surg ICU Other/unknown # of ICU beds.35 > ICU Model closed or mandatory CC consult

23 Onsite Night Coverage Intensivist Other clinician None Nurse-to-Patient Ratio :1-1: :3-1: United States region New England Mid-Atlantic South Atlantic East-North-Central East-South-Central West-North-Central West-South-Central Mountain West Teaching hospital AIDS: autoimmune deficiency syndrome; CC: critical care; Chemo/XRT: chemotherapy and radiation therapy; CV: cardiovascular; GI: gastrointestinal; HD/lymph: Hodgkin s Disease and lymphoma; ICU: intensive care unit; IQR: interquartile range; Leuk/Lymph/ Myel: leukemia, lymphoma, myeloma; Med- Surg: Medical-Surgical; MV: mechanical ventilation; OR/PACU: operating room/post-anesthesia care unit; sd: standard deviation; SDU: stepdown unit a Indicates t test or Wilcoxon rank-sum test for continuous variables; Chi square for categorical variables b Able to match: 5,761 out of 5,763 (>99.9%) overnight extubations for patients with MV 0.5 days; 4,518 out of 4,522 (>99.9%) overnight extubations for patients with MV<0.5 days c This characteristic was not included in the propensity score calculation used for matching patients

24 etable 6. Baseline Characteristics and Outcomes of Propensity-Matched Pairs From APACHE Outcomes Cohort Patients with MV < 12 hours Patients with MV 12 hours Daytime Extubation (7a-6p) Overnight Extubation (7p-6a) P Value a Daytime Extubation (7a-6p) Overnight Extubation (7p-6a) P Value a # of Patients b Characteristics Age (years), mean±sd 62.6± ± ± ± Race White 85.7% 85.7% 75.6% 76.5% Black 8.5% 8.5% 15.7% 15.4% Other 5.8% 5.9% 8.7% 8.1% Female 43.0% 44.4% % 43.4%.90 Admission type Medical 42.2% 38.9% 75.0% 75.1% Elective surgical 49.9% 53.9% 17.0% 17.0% Emergent surgical 7.9% 7.1% 8.0% 7.9% Location prior to ICU Emergency room 20.2% 18.1% 33.7% 32.9% OR/PACU 57.8% 61.0% 25.0% 24.9% Ward 4.9% 4.4% 12.2% 12.1% SDU/telemetry 4.2% 3.9% 7.1% 7.7% Other 12.9% 12.5% 22.0% 22.4% Diagnostic Group Respiratory/thoracic 7.7% 7.6% 18.6% 18.0% Cardiovascular 41.9% 43.6% 27.6% 27.7% Sepsis 4.0% 3.5% 13.9% 14.7% Trauma 5.2% 4.4% 8.7% 7.6% Neurologic 12.1% 12.0% 13.7% 13.6% Metabolic/renal 4.5% 4.3% 5.9% 5.9%

25 Gastrointestinal 17.4% 17.4% 9.3% 10.4% Other/unknown 7.3% 7.3% 2.1% 2.1% Acute physiology score, mean±sd 45.4± ±26.4 > ± ± Comorbidities AIDS 0.2% 0.2% > % 0.3%.53 Myeloma 0.7% 0.7% > % 1.2%.25 Lymphoma 0.4% 0.5% % 1.1%.47 Cirrhosis 2.8% 2.1% % 4.6%.53 Metastatic cancer 3.9% 4.3% % 4.4%.66 Immunosuppressed 6.6% 6.8% % 7.2%.61 Liver failure 1.4% 1.1% % 2.4%.67 MV on ICU admission 81.6% 82.6% % 77.8%.78 Duration of MV (days), mean±sd 0.3± ± ± ± ICU admission year % 23.0% 20.7% 20.7% % 35.5% 34.3% 33.6% % 33.9% 35.7% 36.3% % 7.6% 9.4% 9.4% ICU type Medical ICU 14.1% 13.4% 25.9% 26.6% Surgical ICU 35.8% 37.2% 19.2% 19.7% Medical-Surgical ICU 44.7% 43.8% 47.1% 46.6% Neurologic ICU 5.0% 5.4% 7.0% 6.4% Other/unknown 0.3% 0.3% 0.8% 0.7% United States region Northeast 14.6% 13.7% 16.1% 15.5% Southeast 10.6% 12.3% 17.1% 16.8% Midwest 64.8% 65.0% 53.9% 55.1% West 9.9% 9.0% 12.9% 12.7% Teaching hospital 86.3% 87.4% % 87.7%.51

26 # of ICU beds.88 > % 47.3% 42.6% 42.4% % 23.1% 19.0% 19.4% % 2.8% 4.7% 4.7% % 11.7% 8.6% 8.4% % 4.9% 8.1% 8.1% % 6.8% 9.7% 9.5% % 0.9% 1.8% 1.9% % 1.5% 4.0% 4.5% 6 1.0% 0.9% 1.4% 1.2% Outcomes Reintubation Ever 4.4% 4.7% % 7.9%.28 Within 24 hours 2.3% 2.6% % 5.1%.43 Within 48 hours 3.0% 3.5% % 6.0%.91 Within 96 hours 3.7% 4.3% % 7.1%.62 Mortality ICU 9.0% 9.7% % 28.2% <.001 Hospital 11.5% 12.0% % 32.9% <.001 Length of stay (days), median(iqr) ICU 1.5 (1.0,2.6) 1.4 (0.9,2.7) < (2.4,8.9) 4.0 (2.0,8.5) <.001 Hospital 6.4 (4.2,10.6) 7.2 (4.4,11.9) < (6.2,18.7) 9.3 (5.1,17.0) <.001 AIDS: autoimmune deficiency syndrome; ICU: intensive care unit; IQR: interquartile range; MV: mechanical ventilation; OR/PACU: operating room/postanesthesia care unit; sd: standard deviation; SDU: stepdown unit a Indicates t test or Wilcoxon rank-sum test for continuous variables; Chi square for categorical variables b Able to match: 2,963 out of 2,965 (99.9%) overnight extubations for patients with MV 0.5 days; 2,575 out of 2,710 (95.0%) overnight extubations for patients with MV<0.5 day

27 etable 7. Length of Stay for Propensity-Matched Pairs From Sensitivity Analyses Stratified by Patient Subgroup ICU Length of Stay (days), median (IQR) Hospital Length of Stay (days), median (IQR) Daytime Extubation (7a-6p) Overnight Extubation (7p-6a) P Value Daytime Extubation (7a-6p) Overnight Extubation (7p-6a) Project IMPACT Overnight = 0:00a-4:59a 1.4 (0.9,2.5) 1.1 (0.7,2.1) < (3.0,12.0) 6.5 (3.0,12.0).99 Survivors Hospital 1.4 (0.9,2.4) 1.2 (0.8,2.3) < (4.0,12.0) 7.0 (4.0,12.0) h post-extubation 1.4 (0.9,2.5) 1.2 (0.8,2.3) < (4.0,12.0) 7.0 (4.0,13.0) <.001 Remained extubated >1h 1.4 (0.9,2.4) 1.1 (0.8,2.2) < (4.0,12.0) 7.0 (4.0,12.0).27 P Value MV < 12 hours a APACHE Outcomes Full Cohort 1.5 (1.0,2.6) 1.4 (0.9,2.7) < (4.2,10.6) 7.2 (4.4,11.9) <.001 Overnight = 0:00a-4:59a 1.5 (1.0,2.6) 1.5 (0.8,2.8) (4.4,12.0) 7.3 (4.4,12.5).86 Subgroups Admission type Medical 1.6 (0.9,3.0) 1.5 (0.7,3.0) (2.1,9.2) 5.1 (1.7,10.0).79 Elective Surgical 1.5 (1.0,2.3) 1.2 (0.9,2.3) < (5.3,11.6) 8.0 (5.5,12.2) <.001 Emergent Surgical 1.7 (1.2,3.0) 1.6 (0.8,2.8) (5.6,13.6) 8.1 (5.1,13.3).93 ICU-type Medical ICU 1.3 (0.9,2.4) 1.2 (0.8,3.0) (2.2,7.9) 6.1 (2.1,10.4).022 Surgical ICU 1.5 (1.1,2.5) 1.6 (0.9,2.7) (5.3,12.0) 8.3 (6.0,13.5) <.001 Med-Surg ICU 1.5 (1.0,2.6) 1.2 (0.8,2.5) < (3.5,9.5) 6.4 (4.0,10.3).06 Neuro ICU 2.0 (1.0,4.0) 1.8 (0.8,3.8) (2.6,12.6) 4.9 (2.3,12.5).30 Survivors Hospital 1.6 (1.1,2.7) 1.7 (0.9,2.8) < (4.5,11.3) 7.6 (5.2,12.3) < h post-extubation 1.6 (1.1,2.7) 1.7 (0.9,2.8) < (4.4,11.2) 7.5 (5.1,12.3) <.001 Remained extubated >1h 1.5 (1.0,2.6) 1.4 (0.9,2.7) <.001 6,4 (4.2,10.4) 7.2 (4.4,11.7) <.001

28 Project IMPACT Overnight = 0:00a-4:59a 5.2 (2.7,10.4) 5.4 (2.6,11.6) (7.0,23.5) 14.0 (7.0,25.0).56 Survivors Hospital 4.6 (2.5,9.7) 4.8 (2.5,10.0) (7.0,22.0) 14.0 (8.0,24.0) h post-extubation 4.7 (2.6,9.4) 4.9 (2.6,10.1) (8.0,23.0) 14.0 (8.0,25.0).008 Remained extubated >1h 4.9 (2.6,9.8) 4.7 (2.4,9.8) (7.0,23.0) 13.0 (7.0,23.0).26 MV 12 hours b APACHE Outcomes Full Cohort 4.5 (2.4,8.9) 4.0 (2.0,8.5) < (6.2,18.7) 9.3 (5.1,17.0) <.001 Overnight = 0:00a-4:59a 4.5 (2.2,9.7) 3.5 (1.9,8.7) (6.5,19.8) 9.4 (4.8,17.3) <.001 Subgroups Admission type Medical 5.0 (2.8,10.1) 4.6 (2.3,9.2) < (5.7,19.7) 9.0 (4.4,16.8) <.001 Elective Surgical 2.8 (1.8,5.0) 2.5 (1.3,4.9) (7.2,17.2) 9.9 (6.4,16.1).11 Emergent Surgical 5.5 (2.8,11.4) 4.4 (2.6,10.0) (7.7,22.4) 11.0 (6.0,20.5).10 ICU-type Medical ICU 4.7 (2.6,9.4) 4.7 (2.3,8.6) (5.2,18.1) 8.7 (4.1,15.8).001 Surgical ICU 4.2 (2.3,8.8) 3.7 (2.0,9.0) (7.2,20.3) 11.5 (6.9,19.9).32 Med-Surg ICU 4.0 (2.2,8.1) 3.7 (1.9,7.9) (5.8,16.9) 8.6 (5.0,16.2) <.001 Neuro ICU 6.1 (2.7,10.8) 5.1 (2.6,10.7) (5.9,20.9) 9.8 (4.8,20.4).08 Survivors Hospital 4.1 (2.2,8.0) 4.0 (2.1,8.4) (6.7,18.4) 11.0 (6.5,18.8).83 24h post-extubation 4.3 (2.4,8.6) 4.3 (2.2,8.8) (7.0,19.1) 11.1 (6.5,19.2).20 Remained extubated >1h 4.4 (2.4,8.9) 3.9 (2.0,8.0) < (6.0,18.6) 9.2 (5.0,16.6) <.001 ICU: intensive care unit; IQR: interquartile range; Med-Surg: Medical-Surgical; Neuro: neurological a Project IMPACT overnight =0:00a-4:59a: 1256 out of 1254 (>99%); hospital survivors: 4135 out of 4142 (>99%); survivors 24hrs post-extubation: 4257 out of 4265 (>99%); patients remaining extubated >1hr: 4449 out of 4454 (>99%); APACHE Outcomes full cohort: 2575 out of 2710 overnight extubations matched (95%); overnight =0:00a-4:59a: 763 out of 771 (99%); medical patients: 1007 out of 1011 (>99%); elective surgical patients: 1180 out of 1534 (77%); emergent surgical patients: 163 out of 185 (88%); Medical ICU: 330 out of 349 (95%%); Surgical ICU: 919 out of 1016 (90%); Medical-Surgical ICU: 1079 out of 1199 (90%); Neurological ICU: 115 out of 139 (83%) hospital survivors: 2213 out of 2398 (92%); survivors 24hrs post-extubation: 2310 out of 2489 (93%); patients remaining extubated >1hr: 2551 out of 2689 (95%)

29 b Project IMPACT overnight =0:00a-4:59a: 1256 out of 1256 (100%); hospital survivors: 4834 out of 4835 (>99%); survivors 24hrs post-extubation: 5107 out of 5109 (>99%); patients remaining extubated >1hr: 5549 out of 5551 (>99%); APACHE Outcomes full cohort: 2963 out of 2965 overnight extubations matched (>99%); overnight =0:00a-4:59a: 775 out of 775 (100%); medical patients: 2225 out of 2226 (>99%); elective surgical patients: 459 out of 505 (91%); emergent surgical patients: 234 out of 234 (100%); Medical ICU: 787 out of 788 (>99%%); Surgical ICU: 583 out of 583 (100%); Medical-Surgical ICU: 1380 out of 1382 (>99%); Neurological ICU: 190 out of 190 (100%); hospital survivors: 1989 out of 1990 (>99%); survivors 24hrs post-extubation: 2185 out of 2186 (>99%); patients remaining extubated >1hr: 2892 out of 2893 (>99%)