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Supplementary Table 1. Identification of variables associated with primary and secondary outcome measures among patients presenting for cesarean delivery

Table 1a. Variables associated with opioid consumption during 1st 24 hours following cesarean delivery (primary outcome)

n Median total opioid dose, 1st 24 hours

[IQR] in MME, or rho (ρ) p-value Smoking

Never 1955 22.5 [0, 1087.5] <0.01a

Former 653 37.5 [0, 1140]

Current 281 75 [0, 375]

Unknown 90 22.5 [0, 139.5]

Parity

Nulliparous 1305 30 [0, 1140] 0.03b

Multiparous 1674 30 [0, 718.5]

Gestation type

Singleton 2767 30 [0, 1140] 0.43b

Multiple 212 30 [0, 428.5]

Marital status

Married 1990 22.5 [0, 1140] <0.01b

Other 989 45 [0, 718.5]

Race

White 2585 30 [0, 1140] 0.10b

Other 394 22.5 [0, 718.5]

Comorbidities Depression

Yes 242 60 [0, 1140] <0.001b

No 2737 30 [0, 718.5]

Anxiety

Yes 173 60 [0, 1087.5] <0.001b

No 2806 30 [0, 1140]

PTSD

Yes 48 67.5 [0, 265.5] <0.001b

No 2931 30 [0, 1140]

Chronic pain

Yes 169 60 [0, 265.5] <0.001b

No 2810 30 [0, 1140]

Hypertension

Yes 571 45 [0, 718.5] <0.001b

No 2408 22.5 [0, 1140]

Liver disease

Yes 3 22.5 [0, 82.5] 0.87b

No 2976 30 [0, 1140]

Renal insufficiency

Yes 15 60 [0, 125] 0.32b

No 2964 30 [30, 1140]

Intraoperative intrathecal morphine

Yes 2149 22.5 [0, 375] <0.001b

No 830 39.2 [0, 1140]

Maternal age at delivery 2979 ρ = -0.106 <0.001c

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1b. Variables associated with highest pain score during 1st 24 hours following cesarean delivery (secondary outcome)

N Mean highest pain score, 1st 24 hours

(SD) in NRS, or rho (ρ) p-value Smoking

Never 1955 5.2 (2.1) <0.001a

Former 653 5.9 (2.2)

Current 281 7.4 (2.1)

Unknown 90 5.1 (2.0)

Parity

Nulliparous 1305 5.5 (2.1) 0.03b

Multiparous 1674 5.7 (2.3)

Gestation type

Singleton 2767 5.6 (2.2) 0.41b

Multiple 212 5.5 (2.3)

Marital status

Married 1990 5.3 (2.1) <0.001b

Other 989 6.2 (2.4)

Race

White 2579 5.6 (2.2) 0.41b

Other 394 5.6 (2.4)

Comorbidities Depression

Yes 242 6.6 (2.3) <0.001b

No 2737 5.5 (2.2)

Anxiety

Yes 173 6.8 (2.3) <0.001b

No 2806 5.5 (2.2)

PTSD

Yes 48 7.2 (2.2) <0.001b

No 2931 5.5 (2.2)

Chronic pain

Yes 169 7.0 (2.3) <0.001b

No 2810 5.5 (2.2)

Hypertension

Yes 571 6.1 (2.4) <0.001b

No 2408 5.5 (2.2)

Liver disease

Yes 3 3.7 (0.6) 0.08b

No 2976 5.6 (2.2)

Renal insufficiency

Yes 15 5.3 (2.7) 0.85b

No 2964 5.6 (2.2)

Intraoperative intrathecal morphine

Yes 2149 5.4 (2.1) <0.001b

No 830 6.1 (2.4)

Maternal age at delivery 2979 ρ = -0.131 <0.001c

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1c. Variables associated with length of stay after cesarean delivery (secondary outcome) n Median length of stay [full range] in

hours; or rho (ρ) p-value

Smoking

Never 1950 71 [21, 435] 0.16a

Former 653 71 [27, 206]

Current 280 70 [21,408]

Unknown 90 74 [36, 194]

Parity

Nulliparous 1303 73 [21, 435] <0.001b

Multiparous 1670 70 [21, 248]

Gestation type

Singleton 2762 71 [21, 435] <0.001b

Multiple 211 73 [38, 248]

Marital status

Married 1990 71 [21, 435] <0.01b

Other 989 73 [21, 428]

Race

White 2585 71[21, 428] <0.01b

Other 394 72 [37, 435]

Comorbidities Depression

Yes 242 72 [38, 408] <0.01b

No 2731 71 [21. 435]

Anxiety

Yes 173 73 [38, 215] 0.04b

No 2800 71 [21-435]

PTSD

Yes 48 72 [44, 154] 0.14b

No 2925 71 [21, 435]

Chronic pain

Yes 169 72 [25, 408] 0.25b

No 2804 71 [21, 435]

Hypertension

Yes 571 71 [21, 435] <0.001b

No 2402 70 [21, 428]

Liver disease

Yes 3 60 [51, 73] 0.27b

No 2970 71 [21, 435]

Renal insufficiency

Yes 15 76 [48, 118] <0.01b

No 2958 71 [21, 435]

Intraoperative intrathecal morphine

Yes 2149 70 [25, 206] <0.001b

No 830 72 [21, 435]

Maternal age at delivery 2973 ρ = 0.012 0.50c

Abbreviations: IQR, interquartile range; MME, morphine milligram equivalents; PTSD, posttraumatic stress disorder; NRS, numerical rating scale, 0-10

a: Kruskal Wallis test was used to compare differences in outcome measures among variable categories b: Mann-Whitney U test was used to compare differences in outcome measures between variable categories

c: Spearman’s correlation was used to examine the bivariate relationship between maternal age at delivery and each outcome measure.

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Supplementary Table 2: Details of postoperative and discharge analgesic medications Treatment with opioid agonist

pharmacotherapy

Yesa No Overall

Sample size, n 123 2856 2979

Postoperative opioids dispensed, n (%)b

None 6 (4.9) 882 (30.9) 888 (29.8)

Oxycodone 105 (85.4) 1839 (64.4) 1944 (65.3)

Hydromorphone 29 (23.6) 139 (4.9) 168 (5.6)

Hydromorphone injection 12 (9.8) 100 (3.5) 112 (3.6)

Fentanyl injection 5 (4.1) 85 (3.0) 90 (3.0)

Tramadol 1 (0.8) 28 (1.0) 29 (1.0)

Morphine injection 6 (4.9) 19 (0.7) 26 (0.8)

Hydrocodone-acetaminophen 0 (0.0) 20 (0.7) 20 (0.7)

Fentanyl infusion (critical care) 0 (0.0) 7 (0.2) 7 (0.2)

Oxycodone-acetaminophen 0 (0.0) 5 (0.2) 5 (0.2)

Hydromorphone infusion (critical care) 0 (0.0) 2 (0.1) 2 (0.1)

Received PCA opioids, n (%)d 7 (6.1) 60 (2.2) 67 (2.3)

PCA dose MME, median [IQR]

Postoperative non-opioids, n (%) 63 [42,126] 44 [18,75] 44 [20,84]

Ketorolac 93 (75.6) 2228 (78.0) 2321 (77.9)

Ibuprofen 38 (30.9) 630 (22.1) 668 (22.4)

Acetaminophen 113 (91.9) 2541 (89.0) 2654 (89.1)

Opioids prescribed at discharge, n (%)

Oxycodone 79 (64.2) 2235 (78.2)c 2314 (77.7)

Hydromorphone 33 (26.8) 193 (6.8) 226 (7.6)

Tramadol 0 (0.0) 53 (1.9) 53 (1.8)

Hydrocodone/acetaminophen 0 (0.0) 2 (0.1) 2 (0.1)

None 11 (8.9) 373 (13.1) 384 (12.9)

Abbreviations: PCA, patient controlled analgesia; IQR, interquartile range; MME, morphine milligram equivalents a:Includes 86 patients taking buprenorphine and 37 patients taking methadone b:Unless specified, all medications were given orally. With the exception of those who had no postoperative opioids dispensed, patients received one or more types of opioid medication.

c: 9 patients were also prescribed tramadol

d: PCA data were available for n=114 patients taking opioid agonist pharmacotherapy and n=2756 patients not taking opioid agonist pharmacotherapy

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