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Enhanced Recovery after Surgery (ERAS) at Cesarean to Reduce Postoperative Length of Stay: A Randomized Controlled Trial
Journal Pre-proof Enhanced Recovery after Surgery (ERAS) at Cesarean to Reduce Postoperative Length of Stay: A Randomized Controlled Trial Nickolas C. Teigen, MD, Nicole Sahasrabudhe, MD, Georgios Doulaveris, MD, Xianhong Xie, PhD, Abdissa Negassa, PhD, Jeffrey Bernstein, MD, Peter S. Bernstein, MD, MPH PII:
S0002-9378(19)31234-7
DOI:
https://doi.org/10.1016/j.ajog.2019.10.009
Reference:
YMOB 12926
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 16 July 2019 Revised Date:
1 October 2019
Accepted Date: 16 October 2019
Please cite this article as: Teigen NC, Sahasrabudhe N, Doulaveris G, Xie X, Negassa A, Bernstein J, Bernstein PS, Enhanced Recovery after Surgery (ERAS) at Cesarean to Reduce Postoperative Length of Stay: A Randomized Controlled Trial, American Journal of Obstetrics and Gynecology (2019), doi: https://doi.org/10.1016/j.ajog.2019.10.009. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
1
Enhanced Recovery after Surgery (ERAS) at Cesarean to Reduce Postoperative Length of Stay:
2
A Randomized Controlled Trial
3 4
Nickolas C. Teigen MD1
5
Nicole Sahasrabudhe MD2
6
Georgios Doulaveris MD3,
7
Xianhong Xie PhD4,
8
Abdissa Negassa PhD4,
9
Jeffrey Bernstein MD5,
10
Peter S. Bernstein MD, MPH3
11 12 13
(1) Georgia Perinatal Consultants. Atlanta, GA 30342
14
(2) Kaiser Permanente Southern California, Department of Obstetrics & Gynecology, Downey,
15
CA 90242
16
(3) Albert Einstein College of Medicine / Montefiore Medical Center, Department of Obstetrics
17
& Gynecology and Women's Health, Bronx, NY 10461
18
(4) Albert Einstein College of Medicine / Montefiore Medical Center, Department of
19
Epidemiology and Population Health, Bronx, NY 10461
20
(5) New York University, Department of Anesthesia, New York, NY 10016
21 22
Disclosure: The authors report no conflict of interest. This study received no financial support.
23
CONDENSATION
24
Enhanced recovery after surgery at cesarean did not increase the rate of discharge on
25
postoperative day #2, but did result in improved rates of breastfeeding.
26 27
SHORT TITLE
28
Enhanced Recovery after Surgery (ERAS) at cesarean delivery
29 30
AJOG AT A GLANCE
31
A. Why was this study conducted?
32
To compare whether an enhanced recovery after surgery (ERAS) pathway at cesarean would
33
increase the rate of early hospital discharges and improve postoperative patient satisfaction
34
compared to standard perioperative care.
35
B. What are the key findings?
36
Enhanced Recovery after Surgery (ERAS) at cesarean was not associated with an increase in the
37
number of women discharged early. Evidence that ERAS after cesarean may have the potential
38
to improve outcomes such as day of discharge are suggested by the observed reduction in
39
overall postoperative length of stay, improved patient satisfaction and an increase in
40
breastfeeding rates.
41
C. What does this study add to what is already known?
42
This prospective randomized trial adds to the paucity of literature on ERAS at Cesarean and
43
reaffirms the potential benefits of ERAS at Cesarean to improve postoperative outcomes
44
including overall postoperative length of stay and exclusive breastfeeding rates.
45
ClinicalTrials.gov Identifier: NCT02956616.
46
Date of registration 11/7/2016
47
Date of initial participant enrollment 9/1/2017
48
https://clinicaltrials.gov/ct2/show/NCT02956616?cond=enhanced+recovery+cesarean&rank=1
49 50
Poster presented at the SMFM 39th Annual Meeting, Las Vegas, Nevada. February 11 –
51
February 16, 2019. Final program ID number 977.
52 53
Corresponding author:
54
Nickolas Teigen, MD
55
1000 Johnson Ferry Road NE
56
Atlanta, GA 30342
57
Email: [email protected]
58
617-835-1032
59 60
Word count:
61
Abstract: 348
62
Main text: 2734
63
64
ABSTRACT
65
OBJECTIVE:
66
Our objective was to determine whether an enhanced recovery after surgery (ERAS) pathway at
67
the time of cesarean birth would permit a reduction in postoperative length of stay and
68
improve postoperative patient satisfaction compared to standard perioperative care (SC).
69 70
STUDY DESIGN:
71
Patients undergoing nonemergent cesarean delivery at ≥ 37 weeks of gestation were
72
randomized to ERAS or SC. ERAS involved multiple evidence-based interventions bundled into
73
one protocol. The primary outcome was discharge on postoperative day 2 (POD#2). Secondary
74
outcome variables included pain medication requirements, breastfeeding rates and various
75
measures of patient satisfaction.
76 77
RESULTS:
78
From September 27, 2017 to May 2, 2018, 58 women were randomized to ERAS and 60 to SC.
79
The groups were similar in medical comorbidities, demographic and perioperative
80
characteristics. ERAS was not associated with a significantly increased rate of POD#2 discharges
81
when compared with SC, 8.6% vs. 3.3%, respectively (OR: 2.74, 95% CI 0.51-14.70), but it was
82
associated with a significantly reduced postoperative length of stay (LOS) when compared with
83
standard care, with median LOS of 73.5 [(IQR): 71.08-76.62)] v. 75.5 [(IQR: 72.86-76.84)] hours
84
from surgery, difference in median LOS: (-1.92, 95% CI -3.80 - -0.29). ERAS was not associated
85
with a reduction in postoperative narcotic use, 117.16 ± 54.17 vs. 119.38 ± 47.98 morphine
86
milligram equivalents (Mean difference: -2.22, 95% CI -20.86-16.42). More subjects randomized
87
to the ERAS protocol reported breastfeeding at discharge, 67.2% vs. 48.3% (p=0.046). When
88
patients were surveyed 6 weeks postpartum, those in the ERAS group were more likely to feel
89
that their expectations were met, they achieved their postoperative milestones earlier and to
90
report continued breastfeeding.
91 92
CONCLUSION:
93
ERAS after cesarean was not associated with an increase in the number of women discharged
94
on POD#2, but that may have been related to factors other than patients’ medical readiness for
95
discharge. Evidence that ERAS after cesarean may have the potential to improve outcomes such
96
as day of discharge are suggested by the observed reduction in overall postoperative LOS,
97
improved patient satisfaction and an increase in breastfeeding rates. Even better results may
98
accrue with more provider and patient experience with ERAS.
99
BACKGROUND:
100
Enhanced recovery after surgery (ERAS) involves changes to multiple aspects of perioperative
101
care with the aim of standardizing postoperative patient care, improving patient outcomes,
102
reducing postoperative length of stay, and optimizing patient satisfaction.1 Enhanced recovery
103
pathways have been widely implemented in many different areas of surgery. Initially, these
104
pathways were introduced in colorectal surgery nearly 15 years ago, but have found more
105
widespread usage in surgical specialties including urology, orthopedics, breast surgery and
106
gynecologic surgery. Initiation of enhanced recovery programs have consistently resulted in
107
reduced hospital length of stay, financial savings and improved patient satisfaction.2
108 109
To date, only observational and retrospective studies have been performed looking at the
110
introduction of enhanced recovery pathways at cesarean. In one observational study, the
111
investigators were able to successfully introduce an enhanced recovery program to their
112
obstetrics unit and noted a greater proportion of patients discharged earlier with improved
113
patient satisfaction, without a concomitant increase in readmission rates.3 A recent
114
retrospective study showed that Implementation of an ERAS program for women
115
having planned or unplanned CD was associated with significantly decreased postoperative
116
length of stay (4.86 hours) and significant cost-savings per patient, without increase in hospital
117
readmissions.4
118 119
The components of enhanced recovery pathways vary significantly, though all seek to provide
120
benefits to patients by optimizing the postoperative recovery course through the combination
121
of multiple evidence-based components 5-7. In a previous study aimed at post-cesarean birth
122
discharge timing, comparing early versus usual discharge time, there was no difference
123
observed in the number of maternal readmissions, maternal antibiotic use, maternal well-being
124
and anxiety or depression.8
125 126
Components of enhanced recovery pathways can include standardization of the use of
127
prophylactic antibiotics, venous thromboembolism prophylaxis, minimizing starvation times,
128
use of antiemetics, earlier resumption of feeding postoperatively, use of chewing gum
129
postoperatively, early removal of dressings and urinary catheters, and standing postoperative
130
pain medication orders.9
131 132
Currently, no randomized studies exist in the literature specifically addressing the potential
133
impact of an enhanced recovery pathway among women undergoing cesarean births on
134
postoperative outcomes and postoperative length of stay. Enhanced Recovery after Surgery
135
after cesarean is not practiced at our institution and is not practiced nationally in a consistent
136
fashion.
137 138
Our objective was to determine whether an enhanced recovery after surgery (ERAS) pathway at
139
the time of cesarean birth would permit a reduction in postoperative length of stay and
140
improve postoperative patient satisfaction compared to standard perioperative care (SC).
141 142
METHODS:
143
This was a prospective, randomized clinical trial enrolling pregnant women at the Jack D. Weiler
144
Hospital of Montefiore Medical Center (Bronx, NY) in an urban, academic hospital setting. The
145
study protocol was approved by the institutional review board and written informed consent
146
was obtained from all women prior to enrollment. Women were eligible for enrollment if they
147
had a gestational age of 37 0/7 completed weeks or greater based on the best obstetric
148
estimated due date and were undergoing a scheduled or non-emergent cesarean delivery. Best
149
obstetric estimated due date was used to establish the subject’s due date: either last menstrual
150
period or ultrasound if the last menstrual period was unknown or if a discrepancy with last
151
menstrual period was noted as per American College of Obstetricians and Gynecologists
152
guidelines. Patients were excluded if they were less than 37 weeks of gestation, undergoing an
153
emergent cesarean birth, receiving general anesthesia or had a pregnancy complicated by an
154
active infection, morbidly adherent placenta, pre-existing hypertension or pregnancy induced
155
hypertension preoperatively which would potentially prolong their hospitalization. Patients
156
were also excluded if they had any renal impairment, peptic ulcer disease or known
157
hypersensitivity to ketorolac, all reasons for which they would not be able to receive ketorolac.
158 159
Participants were enrolled by one of the authors on the day of cesarean delivery and after
160
obtaining informed consent were randomized to either an enhanced recovery after surgery
161
(ERAS) protocol for their perioperative care or standard perioperative recovery. Randomization
162
was computer-generated before the first patient was enrolled utilizing Randomization.com with
163
block sizes of four. The randomization allocation was concealed in opaque, identical,
164
sequentially numbered, sealed envelopes. The numbered envelope was opened after written
165
consent was obtained and before the patient entered the operating room. Preoperative
166
surgical preparation and antibiotic prophylaxis followed standard institutional protocols. All
167
women received neuraxial analgesia: spinal, epidural, or combined spinal and epidural.
168
Cesarean delivery techniques followed the preference of the attending surgeon. Following the
169
completion of surgery, computerized postoperative order sets were placed for each patient
170
based on the study arm to which they were previously assigned (Figure 1). Postoperative
171
recovery followed the usual service protocols including ambulation at the patient's discretion,
172
diet initiation at the patient's discretion, urinary catheter removal on postoperative day #1,
173
postoperative dressing removal on postoperative day #1 and ketorolac and narcotic pain
174
medication as needed for pain. Alternatively, the components of the enhanced recovery
175
protocol included several evidence-based recommendations: early ambulation, early diet
176
initiation, early removal of urinary catheter, early removal of postoperative dressing and
177
standing ketorolac for 24 hours postoperatively (Table 1).
178 179
Demographic features, medical comorbidities, and known perioperative risk factors for
180
postoperative complications were recorded. The primary outcome was discharge on
181
postoperative day #2 and was determined by review of the post-cesarean medical record. The
182
discharging provider was not aware of the group allocation. Only the provider who performed
183
the cesarean was aware of the group allocation as they placed the postoperative orders upon
184
completion of the surgery. Discharge timing of the women in our study was based on provider
185
and patient expectations and not based on medical eligibility for discharge. Postoperative Day
186
#2 was selected as the primary outcome as the day of discharge after cesarean in our
187
institution has traditionally been postoperative day #3. Secondary outcomes assessed were
188
postoperative pain medication use, postoperative complications (wound complications, urinary
189
infections, postpartum depression, hospital readmission), breastfeeding initiation determined
190
from the medical record and postoperative telephone survey and breastfeeding continuation
191
determined from postoperative telephone survey. Patient satisfaction and outcome
192
information was determined by telephone contact six weeks after the procedure with a
193
telephone interview and survey.
194 195
To detect a reduction of the primary outcome on early hospital discharges on postoperative day
196
#2 at a rate decrease of 20% with power of 0.80 and a two-tailed alpha of 0.05, 59 women per
197
study group were required for a total of 118 in the study. We assumed a baseline rate of early
198
hospital discharges of 10% in our institution based upon a pilot of implementing early hospital
199
discharges and querying obstetrical providers regarding our institution's practice.
200 201
Postoperative telephone surveys were conducted 6 weeks postpartum to assess patient
202
satisfaction and postoperative experience and complications. Women were asked a series of
203
multiple-choice questions using a Likert scale.
204 205
Demographic characteristics, medical comorbidities and perioperative information were
206
described by study group as mean (SD) or median (range) for continuous variables and
207
frequency (%) for categorical variables as appropriate. Differences between study arms were
208
assessed using t-test or nonparametric equivalent for continuous variables and Pearson chi-
209
square or Fisher exact test for categorical variables as appropriate. Odds ratio (with 95% CI) was
210
used to assess and quantify effect on postoperative complications. Analysis was based on
211
intention to treat principle. All p values were two-sided and a p value ≤ 0.05 was deemed
212
statistically significant. Statistical analysis was performed using STATA (College Station, TX). The
213
study was registered with ClinicalTrials.gov, NCT02956616.
214 215
RESULTS:
216
From September 27, 2017, to May 2, 2018, two hundred twenty-three women were assessed
217
for inclusion, 33 women were excluded as they met one or more exclusion criteria, 69 women
218
declined participation in the study, leaving 121 women that were randomized. Of those
219
randomized, there were 3 protocol breaches assigned to the incorrect study arm, resulting in 58
220
women randomized to enhanced recovery after surgery and 60 women randomized to standard
221
perioperative care (Figure 1). Randomization resulted in groups that were similar in
222
demographic characteristics, medical comorbidities and perioperative characteristics (Table 2).
223 224
Enhanced recovery after surgery at cesarean was not associated with a significantly increased
225
rate of early hospital discharges on postoperative day #2 when compared with standard
226
recovery, 8.6% vs. 3.3% (Effect estimate 2.74, 95% CI 0.51-14.70, p=0.24). We did observe a
227
significantly reduced postoperative length of stay in the enhanced recovery protocol group
228
when compared with standard perioperative care group, 73.5 hours (71.1-76.6) compared with
229
75.5 hours (72.8-76.8), Effect estimate -1.92, p=0.046. No differences were noted in
230
postoperative narcotic requirement, 117.16 ± SD 54.17 vs. 119.38 ± SD 47.98 morphine
231
milligram equivalents (Effect estimate -2.22, 95% CI -20.86-16.42, P=0.81).
232 233
Enhanced recovery after surgery at cesarean was associated with an increase in exclusive
234
breastfeeding postoperatively, with 67.2% exclusively breastfeeding in the enhanced recovery
235
arm compared to 48.3% in the standard recovery group, p=0.046. There were no differences in
236
breastfeeding protocols between the study arms.
237 238
There were no statistically significant differences between the groups when comparing
239
postoperative complications including postoperative infections, gastrointestinal complications,
240
genitourinary complications, wound complications, bleeding complications, hospital
241
readmissions, hypertensive disorder complications or postpartum depression (Table 3).
242 243
Postoperative telephone surveys were conducted at 6 weeks postpartum to assess patient
244
satisfaction and postoperative experience and complications. Women in the Enhanced
245
Recovery arm were more likely to feel that their recovery met expectations, more satisfied with
246
postoperative dietary allowances, more satisfied with their ability to ambulate and more
247
satisfied with their ability to breastfeed. There were however no differences in their perception
248
of preoperative education, postoperative pain control or their perceived ability to bond with
249
their infants (Table 4).
250 251
STRUCTURED DISCUSSION:
252
Principal findings of the study
253
Enhanced recovery after surgery at cesarean was not associated with an increased rate of early
254
hospital discharges on postoperative day #2 compared with standard perioperative care.
255
However, enhanced recovery after surgery at cesarean was associated with a reduction in
256
overall postoperative length of stay compared with standard perioperative care (73.5 hours vs.
257
75.5 hours). Notably, enhanced recovery after surgery at cesarean was also associated with an
258
increase in the percent of women that exclusively breastfed their infants in the postpartum
259
period.
260 261
RESULTS:
262
Although our primary outcome measure did not show an increased rate of early hospital
263
discharges, this is in direct contrast to an enhanced recovery protocol in colorectal surgery
264
which permitted earlier hospital discharges and improved patient satisfaction.10 Adequate
265
comparisons of benefits of enhanced recovery versus standard recovery after cesarean delivery
266
are lacking. An observational study from the United Kingdom was able to successfully introduce
267
an enhanced recovery program to their obstetrics unit and noted a greater proportion of
268
patients discharged earlier, 1.6% on postoperative Day 1 vs. 25.2% on postoperative day 2.11
269
Implementation of this program occurred over the span of 2 years without a concomitant
270
increase in hospital readmissions. Additionally, a retrospective cohort study evaluating
271
implementation of an ERAS pathway for women having cesarean deliveries was associated with
272
decreased postoperative length of stay and cost savings.12
273
However, no prospective randomized trials have been conducted specifically addressing the
274
impact of an enhanced recovery after surgery program on postoperative day of discharge and
275
other postoperative outcomes.
276 277
Clinical Implications
278
Enhanced recovery after surgery at cesarean may have many novel clinical benefits including
279
reducing postoperative length of stay, improving patient satisfaction and increasing the rate of
280
exclusive breastfeeding and reducing postoperative narcotic usage. These interventions may
281
potentially reduce healthcare costs and decrease utilization of hospital resources.
282 283
The specific effect of enhanced recovery on exclusive breastfeeding is unclear. There may be
284
components of enhanced recovery such as encouragement of early ambulation, early feeding
285
and early resumption of normal activity that may help new mothers to feel well after their
286
surgery and more able to exclusively breastfeed their newborns. Specifically addressing this
287
effect of enhanced recovery on breastfeeding may have clinical utility in improving
288
breastfeeding rates in the postpartum period.
289 290
Enhanced recovery after surgery at cesarean was not associated with a reduction in
291
postoperative narcotic usage. We speculate that the lack of reduction in postoperative narcotic
292
use may be multifactorial. Administration of narcotics in the postoperative period can be
293
impacted by the underlying culture within the institution of providing postoperative pain
294
control based on the provider's perception of the patient's need for narcotics and not based on
295
a true objective measure of a patient's narcotic need based on pain scores. Patients in the
296
enhanced recovery arm received ketorolac 15mg intravenously every 6 hours for 24 hours (60
297
mg in total) in comparison to ketorolac administered on an as needed basis in the standard
298
recovery arm. In the control group, patients received a median of 30 (0-60) grams versus 60
299
(60-60) grams (p< 0.001). The significant variability in the administration of ketorolac in the
300
standard recovery arm may reflect that patients and staff were opting to manage postoperative
301
pain without turning to narcotics, and thus mitigating any reduction in postoperative narcotic
302
requirements.
303 304
Research Implications
305
The inability of our study to show a significant difference in the primary outcome measure may
306
be due to limitations of using postoperative day of discharge as a primary outcome measure of
307
medical stability of discharge in our study population. Determination of timing of a patient's
308
medical eligibility for discharge may be confounded by factors such as prolonged neonatal
309
observation in the postpartum period and sociodemographic factors that may preclude early
310
hospital discharge when a woman is deemed medically stable for discharge. Furthermore,
311
discharge timing may be based on patient and provider preferences, expectations, and habits
312
and not based on medical eligibility criteria alone. To show if the difference that we observed in
313
our primary outcome was statistically significant, we performed a post hoc analysis and found
314
that 309 subjects per group would be needed for such a study. Further investigation that
315
includes more in-depth perioperative education materials and a larger study based on our
316
findings including an economic analysis is warranted.
317 318
Strengths and Limitations
319
The main strength of our study was the prospective, randomized study design. The structure of
320
our intervention, however, was not without limitations. Key to an enhanced recovery protocol
321
is perioperative patient education. The perioperative education that was provided in our study
322
related to enhanced recovery was limited to when informed consent was obtained for
323
participation in the study, which was completed just prior to surgery. Given our institutions
324
multiple offices and non-centralized presurgical process, we felt that the only way to achieve
325
standardized education and informed consent was to perform this at the site of where the
326
procedure was occuring, and this was only possible on the day of the procedure. A more
327
thorough perioperative education component may be beneficial at better establishing patient
328
and provider expectations for discharge. In addition, the discharge timing of the women in our
329
study was based on provider and patient expectations and preferences and often not on their
330
medical eligibility. We anticipated 10% of the patients in our standard recovery arm would opt
331
for discharge on postoperative day #2 but actually found that only 3.3% did. It was not possible
332
to determine from the medical record reasons why patients were not discharged on
333
postoperative day #2. An additional limitation of our study was that it was not blinded;
334
performing a blinded study would be difficult to do with this sort of intervention. The majority
335
of the procedures were scheduled and performed during the morning or early afternoon hours
336
(115/118) and therefore we did not anticipate that the time of day that the procedure was
337
performed would have an impact on the primary outcome measure. An additional limitation of
338
our study was that 102 of the eligible 223 subjects were not included in our study because they
339
declined participation. This large rate of declining participation could introduce bias, but that
340
should have been mitigated by the fact that randomization occurred after patients agreed to
341
participate. We do not anticipate that the cesarean delivery technique would add bias because
342
the patients were randomized. An additional limitation of our study is that there may have
343
been cross-over with some patients receiving interventions from the enhanced recovery order
344
set that nursing found potentially beneficial for their patient. Finally, the generalizability of our
345
study may be limited since it was performed at a single center.
346 347
Conclusions
348
In conclusion, we were unable to show an increase in our primary outcome measure of early
349
hospital discharges on postoperative day #2 when patients underwent enhanced recovery after
350
surgery after cesarean in comparison to standard recovery. However, our study was able to
351
show a significant reduction in total postoperative length of stay as well as a significant increase
352
in exclusive breastfeeding with enhanced recovery after surgery which is a novel finding.
353
REFERENCES:
354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395
1. Wilson R, Caughey A, Wood S, Macones G, Wrench I, Huang J, Norman M, Petersson K, Fawcett W, Shalabi M, Metcalfe A, Gramlich L, Nelson G. Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations. American Journal of Obstetrics & Gynecology. 2018 Dec;219(6):523-544. 2. Adamina M, Kehlet H, Tomlinson GA, Senagore AJ, Delaney CP. Enhanced recovery pathways optimize health outcomes and resource utilization: a meta-analysis of randomized controlled trials in colorectal surgery. Surgery. 2011 Jun;149(6):830-840. 3. Wrench, IJ, Allison, A, Galimberti, A, Radley, S, Wilson, MJ. Introduction of enhanced recovery for elective caesarean section enabling next day discharge: a tertiary centre experience. Int J Obstet Anesth. 2015. 24, 2: 124-130. 4. Fay E, Bollag L, Delgado C, Savitsky L, Mills E, Slater J, Hitti J. An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost. American Journal of Obstetrics & Gynecology. JANUARY 2019. S142 5. Wilson, R. Douglas et al. Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations (Part 1) American Journal of Obstetrics & Gynecology, Volume 219, Issue 6, 523.e1 - 523.e15 6. Caughey, Aaron B. et al. Guidelines for intraoperative care in cesarean delivery: Enhanced Recovery After Surgery Society Recommendations (Part 2). American Journal of Obstetrics & Gynecology, Volume 219, Issue 6, 533 - 544 7. Macones, George A. et al.Guidelines for postoperative care in cesarean delivery: Enhanced Recovery After Surgery (ERAS) Society recommendations (part 3)American Journal of Obstetrics & Gynecology, Volume 219 8. Brooten D, Roncoli M, Finkler S, Arnold L, Cohen A., Mennuti M. A randomized trial of early hospital discharge and home follow-up of women having cesarean birth. Obstet Gynecol, 1994. 84: 832-838. 9. Wilson R, Caughey A, Wood S, Macones G, Wrench I, Huang J, Norman M, Petersson K, Fawcett W, Shalabi M, Metcalfe A, Gramlich L, Nelson G. Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations. American Journal of Obstetrics & Gynecology. 2018 Dec;219(6):523-544. 10. Adamina M, Kehlet H, Tomlinson GA, Senagore AJ, Delaney CP. Enhanced recovery pathways optimize health outcomes and resource utilization: a meta-analysis of randomized controlled trials in colorectal surgery. Surgery. 2011 Jun;149(6):830-840.
396 397 398 399 400 401
11. Wrench, IJ, Allison, A, Galimberti, A, Radley, S, Wilson, MJ. Introduction of enhanced recovery for elective caesarean section enabling next day discharge: a tertiary centre experience. Int J Obstet Anesth. 2015. 24, 2: 124-130. 12. Fay, Emily E.Hitti, Jane E.Delgado, Carlos M.Savitsky, Leah M.Mills, Elizabeth B.Slater, JoAnn L.Bollag, Laurent A. et al. American Journal of Obstetrics & Gynecology, 2019.
Figure 1. Algorithm of Randomization
Assessed for eligibility (n=223) Excluded (n=33) Declined (n=69) Randomized (n=121)
Enhanced Recovery
Standard
(n=58)
(n=60) Protocol Deviations (n=3)
Completed Follow-up Survey
Completed Follow-up Survey
(n=56)
(n=53)
Table 1. Enhanced Recovery After Surgery (ERAS) Protocol Chewing gum (Xylitol) to reduce postoperative Ileus Intravenous NSAIDS (Ketorolac) for 24 hours postoperatively to reduce postoperative narcotic use Early initiation of feeding after cesarean: Clear liquid diet immediately in the PACU, Regular diet at 30 minutes Early removal of urinary catheter at 12 hours Early removal of dressing at 6 hours Early mobilization at 12 hours Incentive Spirometry encouraged every 8 hours
Table 2. Patient Demographics, Perioperative Information, and Medical Comorbidities Characteristic
Enhanced Recovery
Standard Recovery
(n=58)
(n=60)
Age (years), mean ± SD
30.43 ± 4.92
31.93 ± 5.43
0.12
BMI (kg/m2), mean ± SD
34.79 ± 6.78
33.34 ± 6.09
0.22
Ethnicity, n (%)
p-value
0.77
Caucasian
4 (6.9)
4 (6.7)
African American
13 (22.4)
16 (26.7)
Hispanic
33 (56.9)
29 (48.3)
Asian
3 (5.2)
2 (3.3)
Other
5 (8.6)
9 (15.0)
Gestational Age (weeks), Median (IQR)
39.0 (39.0-39.3)
39.1 (39.0-39.4)
0.62
Multiparous, n (%)
48 (88.9)
48 (85.7)
0.62
Prior Cesarean Delivery, Median (IQR)
1 (1-2)
1 (1-2)
0.88
Indication for Cesarean Delivery, n (%)
0.66
Prior Cesarean Delivery
50 (86.2)
46 (76.7)
Malpresentation
4 (6.9)
6 (10.0)
Suspected Macrosomia
2 (3.5)
6 (6.7)
Prior Myomectomy
0 (0)
1 (1.7)
Active HSV
0 (0)
1 (1.7)
Twin Gestation
2 (3.5)
1 (1.7)
Primary Elective
0 (0)
1 (1.7)
Estimated Blood Loss (mL), Median (IQR)
800 (700-1000)
800 (800-1000)
0.79
Estimated Blood Loss 1000 mL or greater, n (%)
19 (32.8)
21 (35.0)
0.80
Skin Closure, n (%)
1.00
Monocryl
55 (94.8)
55 (91.7)
Vicryl
0 (0)
1 (1.7)
Staples
3 (5.2)
1 (6.7)
35.34 ± 3.32
35.52 ± 2.97
Preoperative HCT, mean ± SD
0.75
Postoperative Day 1 HCT, mean ± SD
30.52 ± 3.42
30.89 ± 3.31
0.55
Chronic Hypertension, n (%)
0 (0)
0 (0)
NA
Diabetes Mellitus, n (%)
6 (10.3)
12 (20.0)
0.14
Hypertensive Disorder of Pregnancy, n (%)
4 (6.9)
6 (10.0)
0.74
Birthweight, mean ± SD
3409.97 ± 422.74
3348.12 ± 487.69
0.46
Apgar >7 at 5 min, n (%)
55 (94.8)
57 (95.0)
1.00
NICU Admission, n (%)
2 (3.5)
2 (3.3)
1.00
Table 3. Study Outcomes Outcome
Enhanced
Standard
Effect Estimate (95% CI)
p-value
Recovery
Recovery
5 (8.6)
2 (3.3)
2.74 (0.51, 14.70)
0.24
Postoperative length of hospital stay (Hours),
73.58 (71.08-
75.50 (72.86-
-1.92 (-3.80,
0.046
Median (IQR)
76.62)
76.84)
-0.29)
Postoperative Narcotic Use (MME), Mean ± SD
117.16 ± 54.17
119.38 ± 47.98
-2.22 (-20.86, 16.42)
Primary Outcome Discharge on POD#2, n (%) Secondary Outcomes
Breastfeeding, n (%)
0.81 0.046
Breastfeeding
39 (67.2)
29 (48.3)
Bottle
4 (6.9)
2 (3.3)
Both
15 (25.9)
29 (48.3)
Postoperative infection, n (%)
0 (0)
2 (3.3)
0.20 (0.00, 2.53)
0.31
Gastrointestinal Complication, n (%)
1 (1.7)
7 (11.7)
0.13 (0.02, 1.12)
0.06
Wound Complication, n (%)
0 (0)
4(6.7)
0.11 (0.00, 1.04)
0.14
Bleeding Complication, n (%)
19 (32.8)
20 (33.3)
0.97 (0.45, 2.10)
0.95
Postpartum Depression, n (%)
4 (6.9)
10 (16.7)
0.37 (0.11, 1.26)
0.11
Hospital Readmission, n (%)
0 (0)
5 (8.3)
0.09 (0.0, 0.79)
0.10
Hypertensive Disorder complication, n (%)
4 (6.9)
7 (11.7)
0.56 (0.16, 2.03)
0.38
Any Postoperative Complication, n (%)
20 (34.5)
28 (46.7)
0.60 (0.29, 1.26)
0.17
Table 4. Survey Results Enhanced Recovery
Standard Recovery
Do you feel that you were properly educated about the recovery process before your cesarean?, n (%) Strongly Agree
26 (46.4)
18 (34.0)
Agree
30 (53.6)
35 (66.0)
Disagree
0 (0)
0 (0)
Strongly Disagree
0 (0)
0 (0)
0.18
Do you feel that the recovery process after your delivery met your expectations?, n (%) Strongly Disagree
0 (0)
0 (0)
Disagree
0 (0)
0 (3.8)
Agree
16 (28.6)
29 (54.7)
Strongly Agree
40 (71.4)
22 (41.5)
Do you feel that you were prevented from eating or drinking for too long prior to the procedure?, n (%) Strongly Agree
0.003
0.004 0 (0)
0 (0)
Agree
21 (37.5)
36 (67.9)
Disagree
32 (57.1)
16 (30.2)
3 (5.4)
1 (1.9)
Strongly Disagree Did you encounter any postopertive nausea or vomiting after your cesarean?, n (%) Yes No
P-value
0.68 5 (8.9)
6 (11.3)
51 (91.1)
47 (88.7)
Did you encounter any difficulty eating after your cesarean?, n (%)
1.00 Yes
3 (5.4)
2 (3.9)
No
53 (94.6)
50 (96.2)
Approximately, how soon after your cesarean were you able to begin drinking?, n (%) 0-30 min
0.0002 0 (0)
0 (0)
1 (1.8)
1 (1.9)
1h-3h
34 (60.7)
13 (24.5)
4h-6h
21 (37.5)
39 (73.6)
30-60 min
Approximately, how soon after your cesarean were you able to begin eating?, n (%) 0-30 min
0 (0)
0 (0)
30-60 min
0 (0)
0 (0)
1h-3h
6 (10.7)
7 (13.2)
4h-6h
50 (89.3)
46 (86.8)
Approximately how soon after your cesarean were you able to get out of bed?, n (%) 0-2h 2h-4h
0.69
0.01 0 (0)
0 (0)
1 (1.8)
0 (0)
4h-6h
21 (37.5)
9 (17.0)
6h+
34 (60.7)
44 (83.0)
Approximately, how soon after your cesarean were you able to resume your normal activities?, n (%) 0-2h
0 (0)
0 (0)
2h-4h
0 (0)
0 (0)
4h-6h
12 (21.4)
15 (28.3)
6h+
44 (78.6)
38 (71.7)
0.41
Did you encounter any difficulty urinating after your cesarean?, n (%)
0.61 Yes
1 (1.8)
2 (3.9)
No
54 (98.2)
50 (96.2)
Were you able to have skin-to-skin contact with your baby after your cesarean?, n (%) Strongly Agree Agree Disagree Strongly Disagree
0.72 3 (5.4)
1 (1.9)
51 (91.1)
50 (94.3)
2 (3.6)
1 (1.9)
0 (0)
1 (1.9)
Were you satisfied with your ability to bond with your baby after your cesarean?, n (%) Strongly Agree
11 (19.6)
7 (13.2)
Agree
45 (80.4)
45 (84.9)
Disagree
0 (0)
1 (1.9)
Strongly Disagree
0 (0)
0 (0)
Were you satisfied with your ability to breastfeed?, n (%) Strongly Agree
0.44
0.56 8 (14.8)
3 (7.5)
43 (79.6)
36 (90.0)
Disagree
1 (1.9)
1 (2.5)
Strongly Agree
2 (3.7)
0 (0)
Agree
How long after the birth of your baby did you continue to breastfeed?, n (%) Few hours
0 (0)
0 (0)
Few days
0 (0)
4 (7.6)
Few weeks
11 (19.6)
15 (28.3)
Few months
40 (71.4)
20 (37.7)
5 (8.9)
14 (26.4)
No breastfeeding Do you feel that your pain was well-controlled after your cesarean?, n (%) Strongly Agree Agree Disagree Strongly Disagree
0.001
0.52 4 (7.1)
1 (1.9)
51 (91.1)
50 (94.3)
1 (1.8)
2 (3.8)
0 (0)
0 (0)
Did you encounter any infections or complications with your incision after your cesarean?, n (%) Yes No
0.35 1 (1.8)
3 (5.7)
55 (98.2)
50 (94.3)
Did you encounter any urinary infections after your cesarean?, n (%)
NA Yes
0 (0)
0 (0)
No
56 (100)
53 (100)
Were you readmitted to the hospital for any reason after your cesarean?, n (%)
0.20 Yes
1 (1.8)
4 (7.6)
No
55 (98.2)
49 (92.5)
Did you experience postpartum depression?, n (%)
1.00 Yes
2 (3.6)
1 (1.9)
No
54 (96.4)
52 (98.1)
Do you feel that you were satisfied with the overall experience after your cesarean?, n (%) Strongly Agree
28 (50.0)
24 (45.3)
Agree
28 (50.0)
25 (47.2)
Disagree
0 (0)
4 (7.6)
Strongly Disagree
0 (0)
0 (0)
0.15
S0002-9378(19)31234-7
DOI:
https://doi.org/10.1016/j.ajog.2019.10.009
Reference:
YMOB 12926
To appear in:
American Journal of Obstetrics and Gynecology
Received Date: 16 July 2019 Revised Date:
1 October 2019
Accepted Date: 16 October 2019
Please cite this article as: Teigen NC, Sahasrabudhe N, Doulaveris G, Xie X, Negassa A, Bernstein J, Bernstein PS, Enhanced Recovery after Surgery (ERAS) at Cesarean to Reduce Postoperative Length of Stay: A Randomized Controlled Trial, American Journal of Obstetrics and Gynecology (2019), doi: https://doi.org/10.1016/j.ajog.2019.10.009. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.
1
Enhanced Recovery after Surgery (ERAS) at Cesarean to Reduce Postoperative Length of Stay:
2
A Randomized Controlled Trial
3 4
Nickolas C. Teigen MD1
5
Nicole Sahasrabudhe MD2
6
Georgios Doulaveris MD3,
7
Xianhong Xie PhD4,
8
Abdissa Negassa PhD4,
9
Jeffrey Bernstein MD5,
10
Peter S. Bernstein MD, MPH3
11 12 13
(1) Georgia Perinatal Consultants. Atlanta, GA 30342
14
(2) Kaiser Permanente Southern California, Department of Obstetrics & Gynecology, Downey,
15
CA 90242
16
(3) Albert Einstein College of Medicine / Montefiore Medical Center, Department of Obstetrics
17
& Gynecology and Women's Health, Bronx, NY 10461
18
(4) Albert Einstein College of Medicine / Montefiore Medical Center, Department of
19
Epidemiology and Population Health, Bronx, NY 10461
20
(5) New York University, Department of Anesthesia, New York, NY 10016
21 22
Disclosure: The authors report no conflict of interest. This study received no financial support.
23
CONDENSATION
24
Enhanced recovery after surgery at cesarean did not increase the rate of discharge on
25
postoperative day #2, but did result in improved rates of breastfeeding.
26 27
SHORT TITLE
28
Enhanced Recovery after Surgery (ERAS) at cesarean delivery
29 30
AJOG AT A GLANCE
31
A. Why was this study conducted?
32
To compare whether an enhanced recovery after surgery (ERAS) pathway at cesarean would
33
increase the rate of early hospital discharges and improve postoperative patient satisfaction
34
compared to standard perioperative care.
35
B. What are the key findings?
36
Enhanced Recovery after Surgery (ERAS) at cesarean was not associated with an increase in the
37
number of women discharged early. Evidence that ERAS after cesarean may have the potential
38
to improve outcomes such as day of discharge are suggested by the observed reduction in
39
overall postoperative length of stay, improved patient satisfaction and an increase in
40
breastfeeding rates.
41
C. What does this study add to what is already known?
42
This prospective randomized trial adds to the paucity of literature on ERAS at Cesarean and
43
reaffirms the potential benefits of ERAS at Cesarean to improve postoperative outcomes
44
including overall postoperative length of stay and exclusive breastfeeding rates.
45
ClinicalTrials.gov Identifier: NCT02956616.
46
Date of registration 11/7/2016
47
Date of initial participant enrollment 9/1/2017
48
https://clinicaltrials.gov/ct2/show/NCT02956616?cond=enhanced+recovery+cesarean&rank=1
49 50
Poster presented at the SMFM 39th Annual Meeting, Las Vegas, Nevada. February 11 –
51
February 16, 2019. Final program ID number 977.
52 53
Corresponding author:
54
Nickolas Teigen, MD
55
1000 Johnson Ferry Road NE
56
Atlanta, GA 30342
57
Email: [email protected]
58
617-835-1032
59 60
Word count:
61
Abstract: 348
62
Main text: 2734
63
64
ABSTRACT
65
OBJECTIVE:
66
Our objective was to determine whether an enhanced recovery after surgery (ERAS) pathway at
67
the time of cesarean birth would permit a reduction in postoperative length of stay and
68
improve postoperative patient satisfaction compared to standard perioperative care (SC).
69 70
STUDY DESIGN:
71
Patients undergoing nonemergent cesarean delivery at ≥ 37 weeks of gestation were
72
randomized to ERAS or SC. ERAS involved multiple evidence-based interventions bundled into
73
one protocol. The primary outcome was discharge on postoperative day 2 (POD#2). Secondary
74
outcome variables included pain medication requirements, breastfeeding rates and various
75
measures of patient satisfaction.
76 77
RESULTS:
78
From September 27, 2017 to May 2, 2018, 58 women were randomized to ERAS and 60 to SC.
79
The groups were similar in medical comorbidities, demographic and perioperative
80
characteristics. ERAS was not associated with a significantly increased rate of POD#2 discharges
81
when compared with SC, 8.6% vs. 3.3%, respectively (OR: 2.74, 95% CI 0.51-14.70), but it was
82
associated with a significantly reduced postoperative length of stay (LOS) when compared with
83
standard care, with median LOS of 73.5 [(IQR): 71.08-76.62)] v. 75.5 [(IQR: 72.86-76.84)] hours
84
from surgery, difference in median LOS: (-1.92, 95% CI -3.80 - -0.29). ERAS was not associated
85
with a reduction in postoperative narcotic use, 117.16 ± 54.17 vs. 119.38 ± 47.98 morphine
86
milligram equivalents (Mean difference: -2.22, 95% CI -20.86-16.42). More subjects randomized
87
to the ERAS protocol reported breastfeeding at discharge, 67.2% vs. 48.3% (p=0.046). When
88
patients were surveyed 6 weeks postpartum, those in the ERAS group were more likely to feel
89
that their expectations were met, they achieved their postoperative milestones earlier and to
90
report continued breastfeeding.
91 92
CONCLUSION:
93
ERAS after cesarean was not associated with an increase in the number of women discharged
94
on POD#2, but that may have been related to factors other than patients’ medical readiness for
95
discharge. Evidence that ERAS after cesarean may have the potential to improve outcomes such
96
as day of discharge are suggested by the observed reduction in overall postoperative LOS,
97
improved patient satisfaction and an increase in breastfeeding rates. Even better results may
98
accrue with more provider and patient experience with ERAS.
99
BACKGROUND:
100
Enhanced recovery after surgery (ERAS) involves changes to multiple aspects of perioperative
101
care with the aim of standardizing postoperative patient care, improving patient outcomes,
102
reducing postoperative length of stay, and optimizing patient satisfaction.1 Enhanced recovery
103
pathways have been widely implemented in many different areas of surgery. Initially, these
104
pathways were introduced in colorectal surgery nearly 15 years ago, but have found more
105
widespread usage in surgical specialties including urology, orthopedics, breast surgery and
106
gynecologic surgery. Initiation of enhanced recovery programs have consistently resulted in
107
reduced hospital length of stay, financial savings and improved patient satisfaction.2
108 109
To date, only observational and retrospective studies have been performed looking at the
110
introduction of enhanced recovery pathways at cesarean. In one observational study, the
111
investigators were able to successfully introduce an enhanced recovery program to their
112
obstetrics unit and noted a greater proportion of patients discharged earlier with improved
113
patient satisfaction, without a concomitant increase in readmission rates.3 A recent
114
retrospective study showed that Implementation of an ERAS program for women
115
having planned or unplanned CD was associated with significantly decreased postoperative
116
length of stay (4.86 hours) and significant cost-savings per patient, without increase in hospital
117
readmissions.4
118 119
The components of enhanced recovery pathways vary significantly, though all seek to provide
120
benefits to patients by optimizing the postoperative recovery course through the combination
121
of multiple evidence-based components 5-7. In a previous study aimed at post-cesarean birth
122
discharge timing, comparing early versus usual discharge time, there was no difference
123
observed in the number of maternal readmissions, maternal antibiotic use, maternal well-being
124
and anxiety or depression.8
125 126
Components of enhanced recovery pathways can include standardization of the use of
127
prophylactic antibiotics, venous thromboembolism prophylaxis, minimizing starvation times,
128
use of antiemetics, earlier resumption of feeding postoperatively, use of chewing gum
129
postoperatively, early removal of dressings and urinary catheters, and standing postoperative
130
pain medication orders.9
131 132
Currently, no randomized studies exist in the literature specifically addressing the potential
133
impact of an enhanced recovery pathway among women undergoing cesarean births on
134
postoperative outcomes and postoperative length of stay. Enhanced Recovery after Surgery
135
after cesarean is not practiced at our institution and is not practiced nationally in a consistent
136
fashion.
137 138
Our objective was to determine whether an enhanced recovery after surgery (ERAS) pathway at
139
the time of cesarean birth would permit a reduction in postoperative length of stay and
140
improve postoperative patient satisfaction compared to standard perioperative care (SC).
141 142
METHODS:
143
This was a prospective, randomized clinical trial enrolling pregnant women at the Jack D. Weiler
144
Hospital of Montefiore Medical Center (Bronx, NY) in an urban, academic hospital setting. The
145
study protocol was approved by the institutional review board and written informed consent
146
was obtained from all women prior to enrollment. Women were eligible for enrollment if they
147
had a gestational age of 37 0/7 completed weeks or greater based on the best obstetric
148
estimated due date and were undergoing a scheduled or non-emergent cesarean delivery. Best
149
obstetric estimated due date was used to establish the subject’s due date: either last menstrual
150
period or ultrasound if the last menstrual period was unknown or if a discrepancy with last
151
menstrual period was noted as per American College of Obstetricians and Gynecologists
152
guidelines. Patients were excluded if they were less than 37 weeks of gestation, undergoing an
153
emergent cesarean birth, receiving general anesthesia or had a pregnancy complicated by an
154
active infection, morbidly adherent placenta, pre-existing hypertension or pregnancy induced
155
hypertension preoperatively which would potentially prolong their hospitalization. Patients
156
were also excluded if they had any renal impairment, peptic ulcer disease or known
157
hypersensitivity to ketorolac, all reasons for which they would not be able to receive ketorolac.
158 159
Participants were enrolled by one of the authors on the day of cesarean delivery and after
160
obtaining informed consent were randomized to either an enhanced recovery after surgery
161
(ERAS) protocol for their perioperative care or standard perioperative recovery. Randomization
162
was computer-generated before the first patient was enrolled utilizing Randomization.com with
163
block sizes of four. The randomization allocation was concealed in opaque, identical,
164
sequentially numbered, sealed envelopes. The numbered envelope was opened after written
165
consent was obtained and before the patient entered the operating room. Preoperative
166
surgical preparation and antibiotic prophylaxis followed standard institutional protocols. All
167
women received neuraxial analgesia: spinal, epidural, or combined spinal and epidural.
168
Cesarean delivery techniques followed the preference of the attending surgeon. Following the
169
completion of surgery, computerized postoperative order sets were placed for each patient
170
based on the study arm to which they were previously assigned (Figure 1). Postoperative
171
recovery followed the usual service protocols including ambulation at the patient's discretion,
172
diet initiation at the patient's discretion, urinary catheter removal on postoperative day #1,
173
postoperative dressing removal on postoperative day #1 and ketorolac and narcotic pain
174
medication as needed for pain. Alternatively, the components of the enhanced recovery
175
protocol included several evidence-based recommendations: early ambulation, early diet
176
initiation, early removal of urinary catheter, early removal of postoperative dressing and
177
standing ketorolac for 24 hours postoperatively (Table 1).
178 179
Demographic features, medical comorbidities, and known perioperative risk factors for
180
postoperative complications were recorded. The primary outcome was discharge on
181
postoperative day #2 and was determined by review of the post-cesarean medical record. The
182
discharging provider was not aware of the group allocation. Only the provider who performed
183
the cesarean was aware of the group allocation as they placed the postoperative orders upon
184
completion of the surgery. Discharge timing of the women in our study was based on provider
185
and patient expectations and not based on medical eligibility for discharge. Postoperative Day
186
#2 was selected as the primary outcome as the day of discharge after cesarean in our
187
institution has traditionally been postoperative day #3. Secondary outcomes assessed were
188
postoperative pain medication use, postoperative complications (wound complications, urinary
189
infections, postpartum depression, hospital readmission), breastfeeding initiation determined
190
from the medical record and postoperative telephone survey and breastfeeding continuation
191
determined from postoperative telephone survey. Patient satisfaction and outcome
192
information was determined by telephone contact six weeks after the procedure with a
193
telephone interview and survey.
194 195
To detect a reduction of the primary outcome on early hospital discharges on postoperative day
196
#2 at a rate decrease of 20% with power of 0.80 and a two-tailed alpha of 0.05, 59 women per
197
study group were required for a total of 118 in the study. We assumed a baseline rate of early
198
hospital discharges of 10% in our institution based upon a pilot of implementing early hospital
199
discharges and querying obstetrical providers regarding our institution's practice.
200 201
Postoperative telephone surveys were conducted 6 weeks postpartum to assess patient
202
satisfaction and postoperative experience and complications. Women were asked a series of
203
multiple-choice questions using a Likert scale.
204 205
Demographic characteristics, medical comorbidities and perioperative information were
206
described by study group as mean (SD) or median (range) for continuous variables and
207
frequency (%) for categorical variables as appropriate. Differences between study arms were
208
assessed using t-test or nonparametric equivalent for continuous variables and Pearson chi-
209
square or Fisher exact test for categorical variables as appropriate. Odds ratio (with 95% CI) was
210
used to assess and quantify effect on postoperative complications. Analysis was based on
211
intention to treat principle. All p values were two-sided and a p value ≤ 0.05 was deemed
212
statistically significant. Statistical analysis was performed using STATA (College Station, TX). The
213
study was registered with ClinicalTrials.gov, NCT02956616.
214 215
RESULTS:
216
From September 27, 2017, to May 2, 2018, two hundred twenty-three women were assessed
217
for inclusion, 33 women were excluded as they met one or more exclusion criteria, 69 women
218
declined participation in the study, leaving 121 women that were randomized. Of those
219
randomized, there were 3 protocol breaches assigned to the incorrect study arm, resulting in 58
220
women randomized to enhanced recovery after surgery and 60 women randomized to standard
221
perioperative care (Figure 1). Randomization resulted in groups that were similar in
222
demographic characteristics, medical comorbidities and perioperative characteristics (Table 2).
223 224
Enhanced recovery after surgery at cesarean was not associated with a significantly increased
225
rate of early hospital discharges on postoperative day #2 when compared with standard
226
recovery, 8.6% vs. 3.3% (Effect estimate 2.74, 95% CI 0.51-14.70, p=0.24). We did observe a
227
significantly reduced postoperative length of stay in the enhanced recovery protocol group
228
when compared with standard perioperative care group, 73.5 hours (71.1-76.6) compared with
229
75.5 hours (72.8-76.8), Effect estimate -1.92, p=0.046. No differences were noted in
230
postoperative narcotic requirement, 117.16 ± SD 54.17 vs. 119.38 ± SD 47.98 morphine
231
milligram equivalents (Effect estimate -2.22, 95% CI -20.86-16.42, P=0.81).
232 233
Enhanced recovery after surgery at cesarean was associated with an increase in exclusive
234
breastfeeding postoperatively, with 67.2% exclusively breastfeeding in the enhanced recovery
235
arm compared to 48.3% in the standard recovery group, p=0.046. There were no differences in
236
breastfeeding protocols between the study arms.
237 238
There were no statistically significant differences between the groups when comparing
239
postoperative complications including postoperative infections, gastrointestinal complications,
240
genitourinary complications, wound complications, bleeding complications, hospital
241
readmissions, hypertensive disorder complications or postpartum depression (Table 3).
242 243
Postoperative telephone surveys were conducted at 6 weeks postpartum to assess patient
244
satisfaction and postoperative experience and complications. Women in the Enhanced
245
Recovery arm were more likely to feel that their recovery met expectations, more satisfied with
246
postoperative dietary allowances, more satisfied with their ability to ambulate and more
247
satisfied with their ability to breastfeed. There were however no differences in their perception
248
of preoperative education, postoperative pain control or their perceived ability to bond with
249
their infants (Table 4).
250 251
STRUCTURED DISCUSSION:
252
Principal findings of the study
253
Enhanced recovery after surgery at cesarean was not associated with an increased rate of early
254
hospital discharges on postoperative day #2 compared with standard perioperative care.
255
However, enhanced recovery after surgery at cesarean was associated with a reduction in
256
overall postoperative length of stay compared with standard perioperative care (73.5 hours vs.
257
75.5 hours). Notably, enhanced recovery after surgery at cesarean was also associated with an
258
increase in the percent of women that exclusively breastfed their infants in the postpartum
259
period.
260 261
RESULTS:
262
Although our primary outcome measure did not show an increased rate of early hospital
263
discharges, this is in direct contrast to an enhanced recovery protocol in colorectal surgery
264
which permitted earlier hospital discharges and improved patient satisfaction.10 Adequate
265
comparisons of benefits of enhanced recovery versus standard recovery after cesarean delivery
266
are lacking. An observational study from the United Kingdom was able to successfully introduce
267
an enhanced recovery program to their obstetrics unit and noted a greater proportion of
268
patients discharged earlier, 1.6% on postoperative Day 1 vs. 25.2% on postoperative day 2.11
269
Implementation of this program occurred over the span of 2 years without a concomitant
270
increase in hospital readmissions. Additionally, a retrospective cohort study evaluating
271
implementation of an ERAS pathway for women having cesarean deliveries was associated with
272
decreased postoperative length of stay and cost savings.12
273
However, no prospective randomized trials have been conducted specifically addressing the
274
impact of an enhanced recovery after surgery program on postoperative day of discharge and
275
other postoperative outcomes.
276 277
Clinical Implications
278
Enhanced recovery after surgery at cesarean may have many novel clinical benefits including
279
reducing postoperative length of stay, improving patient satisfaction and increasing the rate of
280
exclusive breastfeeding and reducing postoperative narcotic usage. These interventions may
281
potentially reduce healthcare costs and decrease utilization of hospital resources.
282 283
The specific effect of enhanced recovery on exclusive breastfeeding is unclear. There may be
284
components of enhanced recovery such as encouragement of early ambulation, early feeding
285
and early resumption of normal activity that may help new mothers to feel well after their
286
surgery and more able to exclusively breastfeed their newborns. Specifically addressing this
287
effect of enhanced recovery on breastfeeding may have clinical utility in improving
288
breastfeeding rates in the postpartum period.
289 290
Enhanced recovery after surgery at cesarean was not associated with a reduction in
291
postoperative narcotic usage. We speculate that the lack of reduction in postoperative narcotic
292
use may be multifactorial. Administration of narcotics in the postoperative period can be
293
impacted by the underlying culture within the institution of providing postoperative pain
294
control based on the provider's perception of the patient's need for narcotics and not based on
295
a true objective measure of a patient's narcotic need based on pain scores. Patients in the
296
enhanced recovery arm received ketorolac 15mg intravenously every 6 hours for 24 hours (60
297
mg in total) in comparison to ketorolac administered on an as needed basis in the standard
298
recovery arm. In the control group, patients received a median of 30 (0-60) grams versus 60
299
(60-60) grams (p< 0.001). The significant variability in the administration of ketorolac in the
300
standard recovery arm may reflect that patients and staff were opting to manage postoperative
301
pain without turning to narcotics, and thus mitigating any reduction in postoperative narcotic
302
requirements.
303 304
Research Implications
305
The inability of our study to show a significant difference in the primary outcome measure may
306
be due to limitations of using postoperative day of discharge as a primary outcome measure of
307
medical stability of discharge in our study population. Determination of timing of a patient's
308
medical eligibility for discharge may be confounded by factors such as prolonged neonatal
309
observation in the postpartum period and sociodemographic factors that may preclude early
310
hospital discharge when a woman is deemed medically stable for discharge. Furthermore,
311
discharge timing may be based on patient and provider preferences, expectations, and habits
312
and not based on medical eligibility criteria alone. To show if the difference that we observed in
313
our primary outcome was statistically significant, we performed a post hoc analysis and found
314
that 309 subjects per group would be needed for such a study. Further investigation that
315
includes more in-depth perioperative education materials and a larger study based on our
316
findings including an economic analysis is warranted.
317 318
Strengths and Limitations
319
The main strength of our study was the prospective, randomized study design. The structure of
320
our intervention, however, was not without limitations. Key to an enhanced recovery protocol
321
is perioperative patient education. The perioperative education that was provided in our study
322
related to enhanced recovery was limited to when informed consent was obtained for
323
participation in the study, which was completed just prior to surgery. Given our institutions
324
multiple offices and non-centralized presurgical process, we felt that the only way to achieve
325
standardized education and informed consent was to perform this at the site of where the
326
procedure was occuring, and this was only possible on the day of the procedure. A more
327
thorough perioperative education component may be beneficial at better establishing patient
328
and provider expectations for discharge. In addition, the discharge timing of the women in our
329
study was based on provider and patient expectations and preferences and often not on their
330
medical eligibility. We anticipated 10% of the patients in our standard recovery arm would opt
331
for discharge on postoperative day #2 but actually found that only 3.3% did. It was not possible
332
to determine from the medical record reasons why patients were not discharged on
333
postoperative day #2. An additional limitation of our study was that it was not blinded;
334
performing a blinded study would be difficult to do with this sort of intervention. The majority
335
of the procedures were scheduled and performed during the morning or early afternoon hours
336
(115/118) and therefore we did not anticipate that the time of day that the procedure was
337
performed would have an impact on the primary outcome measure. An additional limitation of
338
our study was that 102 of the eligible 223 subjects were not included in our study because they
339
declined participation. This large rate of declining participation could introduce bias, but that
340
should have been mitigated by the fact that randomization occurred after patients agreed to
341
participate. We do not anticipate that the cesarean delivery technique would add bias because
342
the patients were randomized. An additional limitation of our study is that there may have
343
been cross-over with some patients receiving interventions from the enhanced recovery order
344
set that nursing found potentially beneficial for their patient. Finally, the generalizability of our
345
study may be limited since it was performed at a single center.
346 347
Conclusions
348
In conclusion, we were unable to show an increase in our primary outcome measure of early
349
hospital discharges on postoperative day #2 when patients underwent enhanced recovery after
350
surgery after cesarean in comparison to standard recovery. However, our study was able to
351
show a significant reduction in total postoperative length of stay as well as a significant increase
352
in exclusive breastfeeding with enhanced recovery after surgery which is a novel finding.
353
REFERENCES:
354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395
1. Wilson R, Caughey A, Wood S, Macones G, Wrench I, Huang J, Norman M, Petersson K, Fawcett W, Shalabi M, Metcalfe A, Gramlich L, Nelson G. Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations. American Journal of Obstetrics & Gynecology. 2018 Dec;219(6):523-544. 2. Adamina M, Kehlet H, Tomlinson GA, Senagore AJ, Delaney CP. Enhanced recovery pathways optimize health outcomes and resource utilization: a meta-analysis of randomized controlled trials in colorectal surgery. Surgery. 2011 Jun;149(6):830-840. 3. Wrench, IJ, Allison, A, Galimberti, A, Radley, S, Wilson, MJ. Introduction of enhanced recovery for elective caesarean section enabling next day discharge: a tertiary centre experience. Int J Obstet Anesth. 2015. 24, 2: 124-130. 4. Fay E, Bollag L, Delgado C, Savitsky L, Mills E, Slater J, Hitti J. An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost. American Journal of Obstetrics & Gynecology. JANUARY 2019. S142 5. Wilson, R. Douglas et al. Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations (Part 1) American Journal of Obstetrics & Gynecology, Volume 219, Issue 6, 523.e1 - 523.e15 6. Caughey, Aaron B. et al. Guidelines for intraoperative care in cesarean delivery: Enhanced Recovery After Surgery Society Recommendations (Part 2). American Journal of Obstetrics & Gynecology, Volume 219, Issue 6, 533 - 544 7. Macones, George A. et al.Guidelines for postoperative care in cesarean delivery: Enhanced Recovery After Surgery (ERAS) Society recommendations (part 3)American Journal of Obstetrics & Gynecology, Volume 219 8. Brooten D, Roncoli M, Finkler S, Arnold L, Cohen A., Mennuti M. A randomized trial of early hospital discharge and home follow-up of women having cesarean birth. Obstet Gynecol, 1994. 84: 832-838. 9. Wilson R, Caughey A, Wood S, Macones G, Wrench I, Huang J, Norman M, Petersson K, Fawcett W, Shalabi M, Metcalfe A, Gramlich L, Nelson G. Guidelines for Antenatal and Preoperative care in Cesarean Delivery: Enhanced Recovery After Surgery Society Recommendations. American Journal of Obstetrics & Gynecology. 2018 Dec;219(6):523-544. 10. Adamina M, Kehlet H, Tomlinson GA, Senagore AJ, Delaney CP. Enhanced recovery pathways optimize health outcomes and resource utilization: a meta-analysis of randomized controlled trials in colorectal surgery. Surgery. 2011 Jun;149(6):830-840.
396 397 398 399 400 401
11. Wrench, IJ, Allison, A, Galimberti, A, Radley, S, Wilson, MJ. Introduction of enhanced recovery for elective caesarean section enabling next day discharge: a tertiary centre experience. Int J Obstet Anesth. 2015. 24, 2: 124-130. 12. Fay, Emily E.Hitti, Jane E.Delgado, Carlos M.Savitsky, Leah M.Mills, Elizabeth B.Slater, JoAnn L.Bollag, Laurent A. et al. American Journal of Obstetrics & Gynecology, 2019.
Figure 1. Algorithm of Randomization
Assessed for eligibility (n=223) Excluded (n=33) Declined (n=69) Randomized (n=121)
Enhanced Recovery
Standard
(n=58)
(n=60) Protocol Deviations (n=3)
Completed Follow-up Survey
Completed Follow-up Survey
(n=56)
(n=53)
Table 1. Enhanced Recovery After Surgery (ERAS) Protocol Chewing gum (Xylitol) to reduce postoperative Ileus Intravenous NSAIDS (Ketorolac) for 24 hours postoperatively to reduce postoperative narcotic use Early initiation of feeding after cesarean: Clear liquid diet immediately in the PACU, Regular diet at 30 minutes Early removal of urinary catheter at 12 hours Early removal of dressing at 6 hours Early mobilization at 12 hours Incentive Spirometry encouraged every 8 hours
Table 2. Patient Demographics, Perioperative Information, and Medical Comorbidities Characteristic
Enhanced Recovery
Standard Recovery
(n=58)
(n=60)
Age (years), mean ± SD
30.43 ± 4.92
31.93 ± 5.43
0.12
BMI (kg/m2), mean ± SD
34.79 ± 6.78
33.34 ± 6.09
0.22
Ethnicity, n (%)
p-value
0.77
Caucasian
4 (6.9)
4 (6.7)
African American
13 (22.4)
16 (26.7)
Hispanic
33 (56.9)
29 (48.3)
Asian
3 (5.2)
2 (3.3)
Other
5 (8.6)
9 (15.0)
Gestational Age (weeks), Median (IQR)
39.0 (39.0-39.3)
39.1 (39.0-39.4)
0.62
Multiparous, n (%)
48 (88.9)
48 (85.7)
0.62
Prior Cesarean Delivery, Median (IQR)
1 (1-2)
1 (1-2)
0.88
Indication for Cesarean Delivery, n (%)
0.66
Prior Cesarean Delivery
50 (86.2)
46 (76.7)
Malpresentation
4 (6.9)
6 (10.0)
Suspected Macrosomia
2 (3.5)
6 (6.7)
Prior Myomectomy
0 (0)
1 (1.7)
Active HSV
0 (0)
1 (1.7)
Twin Gestation
2 (3.5)
1 (1.7)
Primary Elective
0 (0)
1 (1.7)
Estimated Blood Loss (mL), Median (IQR)
800 (700-1000)
800 (800-1000)
0.79
Estimated Blood Loss 1000 mL or greater, n (%)
19 (32.8)
21 (35.0)
0.80
Skin Closure, n (%)
1.00
Monocryl
55 (94.8)
55 (91.7)
Vicryl
0 (0)
1 (1.7)
Staples
3 (5.2)
1 (6.7)
35.34 ± 3.32
35.52 ± 2.97
Preoperative HCT, mean ± SD
0.75
Postoperative Day 1 HCT, mean ± SD
30.52 ± 3.42
30.89 ± 3.31
0.55
Chronic Hypertension, n (%)
0 (0)
0 (0)
NA
Diabetes Mellitus, n (%)
6 (10.3)
12 (20.0)
0.14
Hypertensive Disorder of Pregnancy, n (%)
4 (6.9)
6 (10.0)
0.74
Birthweight, mean ± SD
3409.97 ± 422.74
3348.12 ± 487.69
0.46
Apgar >7 at 5 min, n (%)
55 (94.8)
57 (95.0)
1.00
NICU Admission, n (%)
2 (3.5)
2 (3.3)
1.00
Table 3. Study Outcomes Outcome
Enhanced
Standard
Effect Estimate (95% CI)
p-value
Recovery
Recovery
5 (8.6)
2 (3.3)
2.74 (0.51, 14.70)
0.24
Postoperative length of hospital stay (Hours),
73.58 (71.08-
75.50 (72.86-
-1.92 (-3.80,
0.046
Median (IQR)
76.62)
76.84)
-0.29)
Postoperative Narcotic Use (MME), Mean ± SD
117.16 ± 54.17
119.38 ± 47.98
-2.22 (-20.86, 16.42)
Primary Outcome Discharge on POD#2, n (%) Secondary Outcomes
Breastfeeding, n (%)
0.81 0.046
Breastfeeding
39 (67.2)
29 (48.3)
Bottle
4 (6.9)
2 (3.3)
Both
15 (25.9)
29 (48.3)
Postoperative infection, n (%)
0 (0)
2 (3.3)
0.20 (0.00, 2.53)
0.31
Gastrointestinal Complication, n (%)
1 (1.7)
7 (11.7)
0.13 (0.02, 1.12)
0.06
Wound Complication, n (%)
0 (0)
4(6.7)
0.11 (0.00, 1.04)
0.14
Bleeding Complication, n (%)
19 (32.8)
20 (33.3)
0.97 (0.45, 2.10)
0.95
Postpartum Depression, n (%)
4 (6.9)
10 (16.7)
0.37 (0.11, 1.26)
0.11
Hospital Readmission, n (%)
0 (0)
5 (8.3)
0.09 (0.0, 0.79)
0.10
Hypertensive Disorder complication, n (%)
4 (6.9)
7 (11.7)
0.56 (0.16, 2.03)
0.38
Any Postoperative Complication, n (%)
20 (34.5)
28 (46.7)
0.60 (0.29, 1.26)
0.17
Table 4. Survey Results Enhanced Recovery
Standard Recovery
Do you feel that you were properly educated about the recovery process before your cesarean?, n (%) Strongly Agree
26 (46.4)
18 (34.0)
Agree
30 (53.6)
35 (66.0)
Disagree
0 (0)
0 (0)
Strongly Disagree
0 (0)
0 (0)
0.18
Do you feel that the recovery process after your delivery met your expectations?, n (%) Strongly Disagree
0 (0)
0 (0)
Disagree
0 (0)
0 (3.8)
Agree
16 (28.6)
29 (54.7)
Strongly Agree
40 (71.4)
22 (41.5)
Do you feel that you were prevented from eating or drinking for too long prior to the procedure?, n (%) Strongly Agree
0.003
0.004 0 (0)
0 (0)
Agree
21 (37.5)
36 (67.9)
Disagree
32 (57.1)
16 (30.2)
3 (5.4)
1 (1.9)
Strongly Disagree Did you encounter any postopertive nausea or vomiting after your cesarean?, n (%) Yes No
P-value
0.68 5 (8.9)
6 (11.3)
51 (91.1)
47 (88.7)
Did you encounter any difficulty eating after your cesarean?, n (%)
1.00 Yes
3 (5.4)
2 (3.9)
No
53 (94.6)
50 (96.2)
Approximately, how soon after your cesarean were you able to begin drinking?, n (%) 0-30 min
0.0002 0 (0)
0 (0)
1 (1.8)
1 (1.9)
1h-3h
34 (60.7)
13 (24.5)
4h-6h
21 (37.5)
39 (73.6)
30-60 min
Approximately, how soon after your cesarean were you able to begin eating?, n (%) 0-30 min
0 (0)
0 (0)
30-60 min
0 (0)
0 (0)
1h-3h
6 (10.7)
7 (13.2)
4h-6h
50 (89.3)
46 (86.8)
Approximately how soon after your cesarean were you able to get out of bed?, n (%) 0-2h 2h-4h
0.69
0.01 0 (0)
0 (0)
1 (1.8)
0 (0)
4h-6h
21 (37.5)
9 (17.0)
6h+
34 (60.7)
44 (83.0)
Approximately, how soon after your cesarean were you able to resume your normal activities?, n (%) 0-2h
0 (0)
0 (0)
2h-4h
0 (0)
0 (0)
4h-6h
12 (21.4)
15 (28.3)
6h+
44 (78.6)
38 (71.7)
0.41
Did you encounter any difficulty urinating after your cesarean?, n (%)
0.61 Yes
1 (1.8)
2 (3.9)
No
54 (98.2)
50 (96.2)
Were you able to have skin-to-skin contact with your baby after your cesarean?, n (%) Strongly Agree Agree Disagree Strongly Disagree
0.72 3 (5.4)
1 (1.9)
51 (91.1)
50 (94.3)
2 (3.6)
1 (1.9)
0 (0)
1 (1.9)
Were you satisfied with your ability to bond with your baby after your cesarean?, n (%) Strongly Agree
11 (19.6)
7 (13.2)
Agree
45 (80.4)
45 (84.9)
Disagree
0 (0)
1 (1.9)
Strongly Disagree
0 (0)
0 (0)
Were you satisfied with your ability to breastfeed?, n (%) Strongly Agree
0.44
0.56 8 (14.8)
3 (7.5)
43 (79.6)
36 (90.0)
Disagree
1 (1.9)
1 (2.5)
Strongly Agree
2 (3.7)
0 (0)
Agree
How long after the birth of your baby did you continue to breastfeed?, n (%) Few hours
0 (0)
0 (0)
Few days
0 (0)
4 (7.6)
Few weeks
11 (19.6)
15 (28.3)
Few months
40 (71.4)
20 (37.7)
5 (8.9)
14 (26.4)
No breastfeeding Do you feel that your pain was well-controlled after your cesarean?, n (%) Strongly Agree Agree Disagree Strongly Disagree
0.001
0.52 4 (7.1)
1 (1.9)
51 (91.1)
50 (94.3)
1 (1.8)
2 (3.8)
0 (0)
0 (0)
Did you encounter any infections or complications with your incision after your cesarean?, n (%) Yes No
0.35 1 (1.8)
3 (5.7)
55 (98.2)
50 (94.3)
Did you encounter any urinary infections after your cesarean?, n (%)
NA Yes
0 (0)
0 (0)
No
56 (100)
53 (100)
Were you readmitted to the hospital for any reason after your cesarean?, n (%)
0.20 Yes
1 (1.8)
4 (7.6)
No
55 (98.2)
49 (92.5)
Did you experience postpartum depression?, n (%)
1.00 Yes
2 (3.6)
1 (1.9)
No
54 (96.4)
52 (98.1)
Do you feel that you were satisfied with the overall experience after your cesarean?, n (%) Strongly Agree
28 (50.0)
24 (45.3)
Agree
28 (50.0)
25 (47.2)
Disagree
0 (0)
4 (7.6)
Strongly Disagree
0 (0)
0 (0)
0.15