27/03/2018 Enhanced recovery after colorectal surgery - UpToDate

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Enhanced recovery after colorectal surgery

Authors: Rocco Ricciardi, MD, MPH, Graham MacKay, MBChB, FRCS, FFST, MD, Girish P Joshi, MB, BS, MD, FFARCSI
Section Editor: Martin Weiser, MD
Deputy Editor: Wenliang Chen, MD, PhD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Oct 30, 2017.

INTRODUCTION — Enhanced recovery programs are evidence-based protocols designed to standardize medical care, improve outcomes, and
lower health care costs. These protocols include evidence-based techniques to minimize surgical trauma and postoperative pain, reduce
complications, improve outcomes, and decrease hospital length of stay, while expediting recovery following elective procedures.

Multimodal enhanced recovery after surgery (ERAS) is an integrated, multidisciplinary approach that requires participation and commitment from
the patient, surgeons, anesthesiologists, pain specialists, nursing staff, physical and occupational therapists, social services, and hospital
administration [1,2]. Initially, ERAS protocols converted many operations performed as inpatient to outpatient "day surgery" procedures. As
experience developed with these protocols, principles of enhanced recovery were applied to increasingly complex procedures to reduce hospital
length of stay and expedite return to baseline health and functional status [2,3].

ERAS protocols have been developed for colorectal surgery patients to reduce physiological stress and postoperative organ dysfunction through
optimization of perioperative care and recovery [1,2,4]. Typically, such protocols include perioperative opioid-sparing analgesia, a laparoscopic
approach for the colorectal resection, avoidance of nasogastric tubes and peritoneal drains, aggressive management of postoperative nausea and
vomiting, and early oral feedings and ambulation (table 1) [5].

This topic will discuss preoperative, intraoperative, and postoperative strategies used in ERAS protocols developed for colorectal surgery. Other
aspects of colorectal surgery are reviewed separately. (See "Overview of colon resection" and "Rectal cancer: Surgical principles" and "Rectal
cancer: Surgical techniques".)

ELEMENTS OF ERAS — The goals of enhanced recovery after surgery (ERAS) protocols include attenuating the surgical stress response and
reducing end organ dysfunction through integrated preoperative, intraoperative, and postoperative pathways. Discharge criteria with ERAS are
similar to those of traditional care, but patients receiving ERAS care meet these discharge criteria sooner [1,2].

ERAS protocols typically include 15 to 20 elements or components combined to form a multimodal pathway. These elements span through the
continuum of the preoperative, intraoperative, and postoperative periods. Separately, individual elements result in modest gains, but when used
together in a complementary fashion, they can decrease postoperative stress responses, thereby reducing duration of postoperative ileus, surgical
complications, incisional pain, recovery time, and length of hospital stay [1,2]. Of the 15 to 20 recommended elements, the relative contribution of
each individual element is unknown [6,7].

Preoperative strategies — Preoperative strategies of ERAS protocols involve medical risk evaluation and patient education including stoma
management, mechanical bowel preparation, and fasting policies.

Medical risk evaluation and interventions — ERAS programs require optimization of medical comorbidities, including cardiovascular,
respiratory, and/or renal disease, as discussed in separate topics:

● (See "Evaluation of cardiac risk prior to noncardiac surgery".)

● (See "Management of cardiac risk for noncardiac surgery".)

● (See "Evaluation of preoperative pulmonary risk".)

● (See "Preanesthesia evaluation for noncardiac surgery".)

Also, social and behavioral factors, such as illicit drug use, tobacco smoking, and alcohol dependency should be addressed.

Patient education and ostomy site selection — Patient education, including discussions regarding ostomy site selection if needed, routine
postoperative care, recovery milestones, and a review of signs and symptoms that warrant a postdischarge surgical evaluation, helps patients
adhere to an ERAS program [4]. (See "Overview of surgical ostomy for fecal diversion", section on 'Preparation and counseling'.)

A United States consensus panel identified a list of warning indicators that should be provided to patients to educate them as to when they should
contact their surgeon or physician following hospital discharge after a colorectal procedure [8]. The warning indicators include:

● Wound drainage

● Wound erythema or changes in the skin around the wound

● No bowel movement or lack of flatus per rectum or ostomy for more than 24 hours

● Increasing abdominal pain

● Vomiting

● Abdominal swelling

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● High ostomy output and/or dark or no urine

● Fever greater than 101.5°F (38.6°C)

● Inability to take in liquids or solid foods for more than 24 hours

● Shortness of breath

● Chest pain

Bowel preparation — We suggest performing mechanical bowel preparation combined with oral antibiotics for all patients undergoing elective
colorectal resection, based on the preponderance of data [9,10]. Others choose to omit bowel preparation [11-13]. Since data regarding bowel
preparation are mixed, mechanical bowel preparation and oral antibiotics will continue to be used at the discretion of the surgeon, regardless of
whether they are a part of an ERAS protocol. Specific aspects of bowel preparation for elective colorectal surgery are discussed further in another
topic. (See "Overview of colon resection", section on 'Bowel preparation'.)

Fasting guidelines — Fasting reduces the risk of aspiration of gastric contents during a general anesthetic by reducing gastric volume and
acidity. Preoperative fasting guidelines have been established by the American Society of Anesthesiologists (ASA) and are based upon
randomized trials and nonrandomized comparative studies [14]. (See "Preoperative fasting guidelines".)

Clear liquids — The ASA guidelines recommend fasting for at least two hours from clear liquids and all other intake, including medicines
[15]. Patients may consume clear liquids include nonalcoholic beverages such as water, juices without pulp, coffee or tea without milk, and
carbohydrate drinks up until two hours before surgery. This approach to fasting helps avoid symptoms of dehydration, hypoglycemia, and caffeine
withdrawal. (See "Preoperative fasting guidelines", section on 'Clear liquids'.)

For ERAS protocols, it is critical to minimize the fasting period; thus, we encourage patients to consume clear liquids until two hours prior to
surgery to remain hydrated. Typically, we advise patients to drink at least two glasses of water before going to bed the night before surgery and
two glasses of water before traveling to the hospital on the morning of surgery. There is no evidence that restriction of the volume of clear liquids is
beneficial [16].

Carbohydrate-rich drink — Many ERAS protocols prescribe a carbohydrate-rich drink two hours prior to surgery. This practice has been
suggested as a method to convert the patient from the "fasted" to the "fed" state, reducing postoperative insulin resistance and postoperative
weight loss [17]. Evidence to support carbohydrate-rich drinks before elective colon surgery is limited [17-19].

Solid foods and milk — The following ASA guidelines are applicable to solid foods and milk (see "Preoperative fasting guidelines", section
on 'Fasting recommendations'):

● Fried or fatty foods or meat – ASA guidelines recommend that patients fast eight hours or more following intake of fried or fatty foods or meat
due to prolonged gastric emptying time.

● Light meal or milk – ASA guidelines recommend that patients fast six hours or more following ingestion of a light meal (eg, toast and tea) or
milk.

Alvimopan — Prolonged postoperative ileus is a main cause of delayed patient recovery, and reducing this complication is a specific objective
of ERAS protocols. The pathogenesis, clinical manifestations, prevention (eg, reduction in opioid use), and management (eg, nasogastric suction,
reduction of opioid use) of ileus are reviewed elsewhere. (See "Postoperative ileus" and "Measures to prevent prolonged postoperative ileus".)

Alvimopan, an oral peripherally acting mu-opioid receptor antagonist (PAM-OR) that has a limited ability to cross the blood-brain barrier, appears
to reduce prolonged ileus after bowel and gynecologic surgery [20]. The benefits of alvimopan are questionable when non-opioid analgesics and
other perioperative opioid-sparing techniques are employed. Alvimopan is used in some ERAS protocols (primarily in the United States) but not
others. When administration is planned, alvimopan should be started preoperatively to be effective. Use of alvimopan to accelerate recovery after
gastrointestinal surgery is further discussed elsewhere. (See "Measures to prevent prolonged postoperative ileus", section on 'Peripheral acting
mu-opioid receptor antagonists'.)

Intraoperative strategies — Intraoperative strategies in ERAS protocols include selection of anesthetic agents and techniques, lung-protective
ventilation, fluid management, temperature regulation, and choice of the surgical approach.

Selection of anesthetic agents — Newer anesthetic agents and advances in agents and techniques have facilitated implementation of ERAS
protocols for colorectal surgery. Long-acting anesthetic agents should be avoided, and multimodal analgesic strategies should be favored. (See
'Pain management' below.)

Typical anesthetic regimens include:

● Use of only short-acting anesthetic agents (eg, propofol, inhaled anesthetics such as sevoflurane or desflurane) that are administered at the
lowest possible doses. (See "General anesthesia: Maintenance and emergence", section on 'Selection of maintenance agents'.)

● Avoidance of premedication with midazolam to reduce the risk of dose-dependent postoperative sedation and respiratory depression,
particularly if opioids are administered [21-23]. (See "General anesthesia: Intravenous induction agents", section on 'Midazolam'.)

● Avoidance of long-acting opioids and reduction of total intraoperative opioid doses (figure 1 and table 2). (See "Perioperative uses of
intravenous opioids in adults".)

● Avoidance of long-acting neuromuscular blocking agents (NMBAs) and use of a peripheral nerve stimulator to avoid profound muscle
paralysis (table 3). Residual effects of an NMBA should be appropriately reversed at the end of surgery (see "General anesthesia:
Maintenance and emergence", section on 'Reverse effects of neuromuscular blocking agents'). Persistent muscle weakness often leads to

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postoperative respiratory complications. (See "Respiratory problems in the post-anesthesia care unit (PACU)", section on 'Neuromuscular
blocking agents'.)

Lung-protective ventilation — The primary goals for intraoperative ventilation are to provide nonharmful ventilation that opens the lungs and
keeps them open into the postoperative period. We suggest the use of lung-protective ventilation for all patients who receive mechanical
ventilation during anesthesia. For most patients, we suggest low tidal volumes of 6 to 8 mL/kg, initial positive end-expiratory pressure (PEEP) of 5
cm H2O (10 cm H2O during laparoscopy), and plateau pressures ≤16 mmHg. (See "Mechanical ventilation during anesthesia in adults", section on
'Lung protective ventilation during anesthesia'.)

Intraoperative fluid management — Intraoperative fluid management is aimed at restoring and maintaining euvolemia. Commonly used
strategies have included (see "Intraoperative fluid management", section on 'Our approach to fluid management'):

● Restrictive fluid therapy (ie, zero-balance approach) avoids fluid overload by replacing only the fluid that is lost during surgery [24]. Given that
the ERAS goals for perioperative fluid management include avoidance of either hypovolemia or excessive fluid administration that may result
in pulmonary complications, we typically use restrictive fluid therapy to minimize fluid administration, rather than the other two strategies [24-
27]. In one randomized multicenter trial of 150 patients undergoing elective colorectal surgery, equivalent postoperative outcomes were noted
with a zero-balance (restrictive) approach compared with a goal-directed approach to fluid therapy [28].

● Goal-directed fluid therapy refers to the administration of fluids to achieve a certain physiologic goal (eg, stroke volume variation, systolic
pressure variation, or pulse pressure variation). If preoperative dehydration is avoided and early postoperative alimentation is emphasized as
part of an ERAS protocol, then goal-directed fluid therapy may be unnecessary because of the low risk of perioperative fluid imbalance [29-
31]. A 2016 meta-analysis of randomized controlled trials of patients undergoing elective major abdominal surgery (2099 patients; 23 studies)
noted no benefit when goal-directed fluid therapy was used within the setting of an ERAS protocol, compared with a fixed-volume regimen
[32].

● Fixed-volume therapy is a traditional approach in which intraoperative fluid administration was based upon predetermined algorithms (eg, 4-2-
1 rule). Fixed-volume therapy can lead to fluid overload.

Temperature regulation — The authors monitor body temperature and routinely use body warmers for all patients undergoing colorectal
surgery. Changes in body temperature that occur with exposure during the procedure and alterations in temperature regulation due to anesthetic
agents may lead to coagulopathy, adverse cardiac events, and decreased resistance to surgical wound infections [33]. Data from a randomized
trial demonstrated that intraoperative hypothermia prolonged the duration of time in the recovery room compared with routine thermal
management (mean 94 versus 53 minutes) [34]. Hypothermia is most likely to occur when procedures are longer than two hours, in older adults, in
those with little body fat, and in those with comorbid illnesses [34-37]. (See "Perioperative temperature management", section on 'Intraoperative
hypothermia' and "Perioperative temperature management", section on 'Postoperative temperature derangements'.)

Laparosopic surgery — Minimally invasive techniques are central to ERAS protocols because they decrease inflammatory mediator release,
improve pulmonary function, expedite return of bowel function, and reduce length of hospital stay [38-45]. For patients with malignant diseases,
the oncologic outcomes of laparoscopic colon surgery are comparable to those of open surgery. (See "Surgical resection of primary colon cancer",
section on 'Open versus laparoscopic colectomy'.)

Several randomized trials have compared laparoscopic and open colorectal surgery with the utilization of an ERAS protocol. A meta-analysis of
these trials concluded that laparoscopic surgery reduced both the length of hospital stay and the rate of complications [46].

When laparoscopic procedures are converted to open surgery, patient outcomes are not necessarily compromised. In a retrospective review of
2483 patients undergoing laparoscopic colorectal procedures, 11 percent required a conversion. Those who converted had similar 30-day mortality
(0.4 versus 0 percent) and overall morbidity rates (27 percent in both groups) compared with those who completed the procedure laparoscopically
[47].

Peritoneal drains — Peritoneal drains are not included in ERAS protocols. In the elective setting, drains do not reduce postoperative morbidity
or mortality or ameliorate the effect of anastomotic leakage. Data are limited on the use of peritoneal drains in emergency settings. Further
discussion on the use of drains can be found elsewhere. (See "Principles of abdominal wall closure", section on 'Drains' and "Traumatic
gastrointestinal injury in the adult patient", section on 'Role of drains'.)

Postoperative strategies — Postoperative goals in ERAS protocols include prevention and relief of pain or nausea and vomiting, and facilitation
of early nutrition and mobilization.

Pain management — Optimal perioperative pain management enhances recovery after colorectal surgery by facilitating postoperative
ambulation and rehabilitation. Procedure-specific multimodal analgesia that minimizes opioid use is ideal [48,49].

● For patients undergoing laparoscopic colorectal procedures, we use non-opioid analgesics (eg, acetaminophen and a nonsteroidal anti-
inflammatory drug [NSAID] or cyclooxygenase [COX]-2 specific inhibitor) in combination with local anesthetic infiltration at the portal sites [50].

In a nonrandomized study of laparoscopic colorectal surgery, local infiltration with a long-acting local anesthetic (liposomal bupivacaine) was
associated with reduced opioid use, a shorter length of stay (mean three versus four days), and lower overall cost [51]. For cost reasons,
others do not locally infiltrate liposomal bupivacaine during major abdominal surgery but reserve it for use in a transversus abdominis plane
(TAP) block [52].

Acetaminophen, ibuprofen, and ketorolac are available in intravenous forms for patients who do not yet tolerate oral formulations. It remains
controversial whether perioperative use of NSAIDs increases the risk of anastomotic leak. (See "Management of anastomotic complications of
colorectal surgery", section on 'Controversial, inconclusive, or negative'.)

Also, we usually administer dexamethasone 8 to 10 mg for both analgesic and antiemetic prophylaxis. Thoracic epidural analgesia is no
longer recommended after laparoscopic surgery because it could potentially delay ambulation and hospital discharge without providing any
additional benefit in pain control [50,53-55].
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● For patients undergoing open colorectal procedures, we typically use a transversus abdominis plane block (TAP block) or surgical site
infiltration, in combination with non-opioid analgesic agents [48]. (See "Management of acute perioperative pain".)

Postoperative fluid management — Following major colorectal surgery, there is little consensus regarding optimal strategies for fluid
management. Intravenous fluid administration should be discontinued as soon as the patient can tolerate oral liquids. Before oral intake is allowed,
patients typically receive an infusion of a balanced salt solution (eg, Lactated Ringers) at 50 mL/hour, with boluses of 100 mL if necessary to treat
hemodynamic instability and/or inadequate urine output (UO).

Although maintenance of a minimum hourly UO of 0.5 mL/kg is a common goal, limited data support this practice. In one randomized trial in 40
patients without significant risk factors for kidney injury, fluid was administered to maintain a minimum UO of either 0.2 or 0.5 mL/kg per hour
during and after major abdominal surgery (from the time of anesthetic induction until the second postoperative day) [56]. While patients in the low-
target UO group received less fluid than the high-target UO group (3170 versus 5490 mL), laboratory measurements of kidney function and other
outcomes were not different. Thus, patients without risk factors for acute kidney injury may be managed with less postoperative fluid, but it is not
known whether this practice can reduce postoperative complications or length of hospital stay.

Diet — ERAS programs incorporate resumption of a diet within a few hours after surgery and can be supplemented with high-calorie drinks to
minimize the negative protein balance after surgery. This is in contrast to the traditional approach where oral feedings were withheld until signs of
bowel activity (eg, bowel sounds, flatus, bowel movement) were evident. In one study, the presence of bowel sounds, flatus, or bowel movement
after major abdominal surgery was not predictive of tolerance of oral intake [57]. Details regarding postoperative nutritional support are discussed
separately. (See "Overview of perioperative nutritional support".)

Early mobilization — Early mobilization is a key element of ERAS protocols for all postoperative patients capable of ambulation [58]. Early
mobilization is essential to reducing the risk of postoperative pneumonia [59,60] and venous thromboembolism (see "Overview of the causes of
venous thrombosis", section on 'Surgery'). Involving hospital resources such as physical and occupational therapists can help achieve the goal of
early mobilization.

Avoidance of nasogastric tubes — Nasogastric tubes, once a mainstay of colon and rectal surgery, are associated with patient discomfort
and a delay in time for oral intake and are not included in the ERAS protocols for most elective patients [61-63]. The authors do not use
nasogastric tubes in elective colorectal surgery. The indications, management, and controversies associated with nasogastric tubes are discussed
separately. (See "Nasogastric and nasoenteric tubes".)

Early urinary catheter removal — To aid with early mobilization, urinary catheters should be removed as early as possible, a process that also
reduces the incidence of urinary tract infection after surgery. (See "Catheter-associated urinary tract infection in adults", section on 'Catheter
management' and "Placement and management of urinary bladder catheters in adults", section on 'Catheter removal'.)

Predicting infective complication — C-reactive protein (CRP) is effective as an early predictor of infective complications after colorectal
surgery. Postoperative day 3 CRP >150 mg/L or persistent elevation of CRP should increase suspicion of an infective complication. Conversely,
CRP levels below this threshold are highly predictive of an uncomplicated recovery and are commonly used in ERAS protocols to guide discharge
[64,65].

Early discharge — The goal of ERAS programs is an accelerated recovery and return to normal activity. Hospital stay (typically ≤5 days) is
often used as a surrogate marker of recovery but is not the only focus of the protocol [66]. In comparison, the mean length of stay of a traditional
practice is >5 to 9 days.

OUTCOMES — Data from observational studies and randomized trials show that enhanced recovery after surgery (ERAS) protocols are
associated with reduced hospital length of stay (LOS) and morbidity, faster recovery, comparable or reduced readmission rate, and cost savings
compared with traditional care in both older and young adults [3,10,67-74].

Length of stay and morbidity — Contemporary series of colorectal surgery using ERAS protocols report hospital LOS ranging from three to five
days [71,75-81]. In a 2014 systematic review and meta-analysis of 16 randomized trials of elective colorectal surgery, those managed with versus
without an ERAS program had a significantly reduced LOS (weighed mean difference -2.28 days; 95% CI -3.09 to -1.47 days) and reduced overall
morbidity (relative ratio [RR] 0.60, 95% CI 0.46-0.76) and nonsurgical complications (RR 0.40, 95% CI 0.27-0.61) but not a higher readmission
rate [82]. A 2014 meta-analysis of 38 trials across all surgical specialities, including but not limited to colorectal surgery, reached a very similar
conclusion that ERAS reduced both complications and LOS [83].

In-hospital morbidity rates may be lower secondary to the shorter LOS. Further prospective trials are needed to assess 30-day morbidities.
However, in a 2017 meta-analysis of randomized trials of abdominal or pelvic surgery utilizing ERAS protocols, a subgroup analysis of colorectal
surgery trials demonstrated a significant reduction in the rates of health care-associated lung, urinary tract, and surgical site infections [84].

Faster recovery — In addition to shorter hospital LOS and lower morbidity, several other favorable postoperative outcomes of "enhanced" or
faster recovery have been attributed to ERAS protocols in observational studies:

● Reduced duration of an ileus [85].

● Preservation of lean body mass and exercise performance [86].

● Improved grip strength suggesting overall improvement in muscle function [76].

● Earlier resumption of normal activities, reduced need for daytime sleep, and no increased use of primary care services [87].

Readmission rates — Early discharge (LOS ≤5 days) is the goal of ERAS protocols, but the benefit of early discharge may be offset by a higher
rate of hospital readmissions [66,72,82,88,89]. Early studies suggested that patients managed with ERAS programs had an increased readmission
rate compared with traditional practice [68,69]. However, a meta-analysis of six later randomized trials and prospective studies found that the rate
of readmission was not significantly different after ERAS versus traditional recovery programs (RR 1.17, 95% CI 0.73-1.86) [72].

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Whether early discharge is associated with higher readmission rates and the optimal discharge day to avoid hospital readmission have not been
clearly established. As an example, in a retrospective review of the United States National Medicare (MEDPAR) database, which included 477,461
patients undergoing a colectomy, very early discharge (defined as median LOS ≤4 days [21.3 versus 15.7 percent]), but not early discharge
(defined as median LOS ≤5 days [16.3 versus 15.7 percent]) was associated with higher readmission rates compared with usual practice [66].

Cost — For an ERAS protocol to be financially justified, the cost (eg, from a laparoscopic procedure) must be balanced with savings from a
shorter hospital admission, with fewer readmissions and complications. Prospective trials to analyze the costs and benefits of ERAS programs are
in progress, with initial data suggesting an overall cost benefit [90-94].

Older patients — Critics of ERAS protocols cite selection bias for younger and healthier patients; however, ERAS protocols for elective colorectal
resection have been shown to benefit older adults as well as younger patients. In the study mentioned above that used the MEDPAR database,
patients were older than 65 years and were effectively treated with use of an ERAS protocol [66]. A prospective study of 87 patients aged 70 years
and older reported a mean hospital stay of 3.9 days, with most (90 percent) tolerating early postoperative feedings [95].

Urgent colorectal surgery — Most existing ERAS programs have been designed, validated, and implemented for elective colorectal surgery. One
small study found that although the compliance rate was lower with urgent surgery, elements of an ERAS protocol designed for elective surgery
were also applicable to urgent surgery [96].

QUALITY IMPROVEMENT INITIATIVES — In 2010, the Enhanced Recovery After Surgery (ERAS) Society was founded to identify and
implement methods to reduce the discrepancies noted between actual surgical practice and best practice. The ERAS Society has developed
multimodal enhanced recovery care pathways, an implementation program, and an interactive audit system. The model is available to participants
as a quality improvement initiative, providing detailed reports and feedback to assist surgeons and institutions with enhanced recovery for their
patients [97].

Other noteworthy organizations for ERAS include the American Society of Enhanced Recovery (ASER) [98] and the Agency for Healthcare
Research and Quality (AHRQ) Patient Safety program [99].

SUMMARY AND RECOMMENDATIONS — Enhanced recovery after surgery (ERAS) programs are evidence-based protocols designed to
standardize medical care, improve outcomes, and lower health care costs.

● ERAS protocols for colorectal surgical patients were developed to reduce inpatient hospital costs through refinements in preoperative,
intraoperative, and postoperative strategies. Organization and effectiveness of an ERAS protocol requires participation and commitment from
a multidisciplinary team, including surgeons, anesthesiologists, nursing staff, social services, and hospital administration. (See 'Introduction'
above.)

● We suggest the ERAS approach for patients undergoing elective colorectal operations (Grade 2B). (See 'Outcomes' above.)

● The elements of an ERAS protocol include (table 1):

• Preoperative pathway strategies (eg, medical risk evaluation, patient education including stoma management, mechanical bowel
preparation plus oral antibiotics, and appropriate fasting guidelines). (See 'Preoperative strategies' above.)

• Intraoperative pathway strategies (eg, selection of short-acting anesthetic agents, lung-protective ventilation, restrictive fluid therapy,
temperature regulation, and laparoscopic surgery). (See 'Intraoperative strategies' above.)

• Postoperative pathway strategies (eg, multimodal analgesia with an emphasis on non-opioid pain management, appropriate fluid
management, early oral feeding and mobilization, avoidance of nasogastric tubes, early removal of urinary catheter, and early discharge).
(See 'Postoperative strategies' above.)

● Use of ERAS protocols is associated with reduced hospital length of stay and morbidity, faster recovery, comparable or reduced readmission
rate, and cost savings compared with traditional care in both old and young patients. (See 'Outcomes' above.)

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97. http://erassociety.org/ (Accessed on June 05, 2017).
98. http://aserhq.org/protocols/ (Accessed on August 09, 2017).
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GRAPHICS

Enhanced recovery after surgery protocol for colorectal procedures in adults

Preoperative period
Patient education (including stoma site selection)

Optimization of medical comorbidities

Mechanical bowel preparation and oral antibiotics

Fasting from fried or fatty foods or meat for eight hours

Fasting from light meals and non-clear liquids (eg, tea and toast, juice with pulp, milk) for six hours

Fasting from clear liquids (excludes alcoholic beverages, beverages with milk, juice with pulp) for two hours

No premedication

Carbohydrate drink two hours prior to the procedure (optional)

Intraoperative period
Thromboprophylaxis

Antibiotic prophylaxis

Normothermia

Fluid optimization

Minimally invasive surgical approach

Avoid nasogastric tubes

Avoid intra-abdominal or perineal drains (except in settings such as colonic spillage or purulent drainage)

Postoperative period
Enteral nutrition beginning on postoperative day 1

High-calorie supplements twice daily

Multimodal analgesia (eg, transverse abdominis block and opioid-sparing pain medications)

Multimodal antiemetic regimen

Early removal of urinary catheter, typically on postoperative day 1

Early mobilization using a structured program, typically on the evening of the procedure

This ERAS protocol is an example of a protocol that is used for patients after elective colorectal surgery.

ERAS: enhanced recovery after surgery.

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Context-sensitive half time for opioids

Context-sensitive half time, or time in minutes to a 50 percent decrease in effect-site concentration (Ce)
after an infusion is stopped.

Reproduced from: Ogura T, Egan TD. Opioid Agonists and Antagonists. In: Pharmacologyand Physiology for
Anesthesia: Foundations and Clinical Application, Hemmings HC, Egan TD (Eds), Philadelphia, PA, Elsevier, 2013.
Illustration used with the permission of Elsevier Inc. All rights reserved.

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Pharmacokinetics for IV opioids used in the perioperative setting

Duration
Speed of Context- of action
Metabolism Drug-drug
Drug Drug class onset sensitive half and Comments
and clearance interactions
(minutes) time* elimination
half life

Fentanyl Phenylpiperidine 4 to 6 May be prolonged Duration of Metabolized in liver Synergistic effects if Longest duration of
opioid minutes and continues to action (after a by cytochrome coadministered with action in the
increase as bolus dose): CYP3A4 to other anesthetic phenylpiperidine
duration of infusion 30 to 45 norfentanyl (an agents. family.
increases (for minutes. inactive metabolite). Caution with Pharmacokinetics
example, after Elimination half Metabolite excreted coadministered unaffected by renal
infusion for 200 life: 3 to 6 by kidney with serotonergic agents or hepatic
minutes, hours. clearance 8 mL/kg due to increased insufficiency.
approximately 200 per minute. risk of serotonin
more minutes are syndrome.
necessary to
Caution with
achieve a 50%
CYP3A4 inhibitors
decrease in effect
(eg, diltiazem,
site concentration).
ritonavir,
voriconazole),
which may increase
plasma levels of
fentanyl.

Remifentanil Phenylpiperidine 1 to 2 Approximately 5 Duration of Metabolized by Synergistic effects if Fastest onset and
opioid minutes minutes. action: 3 to 10 nonspecific coadministered with shortest duration of
Duration of action minutes. esterases in plasma, other anesthetic action compared
is not affected by Elimination half red blood cells, and agents. with other opioids.
duration of life: 10 to 20 interstitial tissue to Higher incidence of
infusion. minutes. remifentanil acid hypotension
(an inactive compared with other
metabolite). opioids.
Metabolite excreted Need for alternative
by kidney with analgesic agent or
clearance of 40 technique during
mL/kg per minute. emergence and the
postoperative period
if pain is
anticipated.
In selected
circumstances, may
be used for a
remifentanil
intubation
technique.

Sufentanil Phenylpiperidine 3 to 5 Context-sensitive Elimination half Metabolized in liver Synergistic effects if Used for longer
opioid minutes half time plateaus life: 2 to 4 and small coadministered with procedures when
at 30 to 45 minutes hours. intestines. other anesthetic continuous opioid
(shorter than Metabolites agents. administration and a
fentanyl). excreted by kidney postoperative
with renal clearance analgesic effect are
12 mL/kg per desirable, and rapid
minute. emergence is not
needed.
Likelihood of muscle
and chest wall
rigidity, particularly
if administered
rapidly or in high
doses.

Alfentanil Phenylpiperidine 1 to 3 Context-sensitive Elimination half Metabolized in liver Synergistic effects if Avoided in patients
opioid minutes half time plateaus life: 1.5 to 2 by cytochrome coadministered with with risk factors for
at 30 to 45 minutes hours. CYP3A4 to other anesthetic seizures due to focal
(shorter than noralfentanil (an agents. activation of the
fentanyl). inactive metabolite). Similar to fentanyl, cerebral cortex in
Excreted by kidney use caution with susceptible patients.
with renal clearance CYP3A4 inhibitors Hepatic metabolism
5 mL/kg per (eg, diltiazem, less predictable
minute. ritonavir, compared with
voriconazole), fentanyl due to
which may increase inter-individual
plasma levels of variability in activity
alfentanil. of hepatic CYP3A4.

Hydromorphone Semi-synthetic Within 10 N/A Duration of Metabolized in liver Synergistic effects if Suitable for
phenanthrene minutes action: 2.4 to glucuronide coadministered with treatment of
opioid hours. metabolites. other anesthetic postoperative pain.
Elimination half Hydromorphone-3- agents. Caution with use in
life: 2.3 hours. glucoronide patients with renal

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excreted by kidney; insufficiency due to
may accumulate likely accumulation
with renal of hydromorphone-
insufficiency. 3-glucoronide,
which causes
neuroexcitation that
may result in
myoclonus or
exacerbation of
seizures.

Morphine Phenanthrene Within 20 N/A Duration of Metabolized in liver Synergistic effects if Suitable for
opioid minutes action: 4 to 6 to glucuronide coadministered with treatment of
hours (but up metabolites other anesthetic postoperative pain.
to 7 hours for (morphine-6- agents. Unsuitable for use in
active glucoronide and patients with renal
morphine-6- morphine 3- insufficiency due to
glucuronide glucoronide). likely accumulation
metabolite). Morphine-6- of morphine-6-
Elimination half glucoronide is an glucoronide, which
life: 2 to 3 active metabolite produces ongoing
hours, but 7 and is excreted by analgesia, and
hours for kidney with renal possible
active clearance 2.2 mL/kg neuroexcitation that
metabolite. per minute; may may result in
accumulate with myoclonus or
renal insufficiency. exacerbation of
seizures.

N/A: not applicable.

* Context-sensitive half time is the time in minutes required for a 50% decrease in effect site concentration after the infusion is discontinued.

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Properties of neuromuscular blocking agents

Agent* Vecuronium Rocuronium Pancuronium Mivacurium Atracurium Cisatracurium Succinylcholine

Type (structure) Non- Non- Non-depolarizing Non-depolarizing Non-depolarizing Non-depolarizing Depolarizing

depolarizing depolarizing

Type (duration) Intermediate Intermediate Long Short Intermediate Intermediate Ultrashort

Potency - ED 95 0.04 0.30 0.07 0.08 0.21 0.04 to 0.05 0.25 to 0.30
(mg/kg)

Intubating dose 0.10 to 0.20 0.60 to 1.00 0.08 to 0.12 0.20 0.50 to 0.60 0.15 to 0.20 0.60 to 1.50
(mg/kg) (1.20 with RSII
dose)

Onset time (min) 3 to 4 1 to 2 2 to 3 3 to 4 3 to 5 4 to 6 1

Time to 25% 20 to 35 30 to 50 (60 to 60 to 120 15 to 20 20 to 35 30 to 60 5 to 10

recovery (min) 80 with RSII
dose)

Elimination half-life (min)

Normal organ 50 to 60 60 to 100 100 to 130 2 to 2.5 21 23 to 30 <1

function

Renal Mild increase 100 to 300 Increased x2 3 to 4 21 Mild increase <1

impairment

Hepatic Significant 120 to 400 Increased x2 3 to 6 21 23 to 30 <1

impairment increase

Maintenance 0.01 0.10 0.02 0.10 0.10 0.01 N/A

dose (mg/kg)

Infusion dose 1 to 2 5 to 12 20 to 40 (not 5 to 8 10 to 20 1 to 3

(mcg/kg/min) recommended)

Elimination Renal 10 to Renal 30%; Renal 40 to 70%; Plasma Renal 10%; Hoffman 30%; Butyrylcholinesterase
route/metabolism 50%; hepatic 70% hepatic 20% cholinesterase (70% Hoffman 30%; ester hydrolysis (plasma
hepatic 30 to of succinylcholine ester hydrolysis 60% cholinesterase,
50% rate) 60% pseudocholinesterase)

Active 3-desacetyl- 17-desacetyl- 3-OH- No active No active No active No active metabolites

metabolites vecuronium rocuronium pancuronium; 17- metabolites metabolites metabolites
(minimal) OH-pancuronium

Side effects Vagal blockade Minimal Vagal block Histamine release Histamine None; histamine Myalgia; bradycardia/
with large doses (tachycardia), release; release at high asystole in children or
catecholamine laudanosine and doses with repeated dosing;
release acrylates dual (phase II,
production competitive) block;
anaphylaxis

Contraindications None None Short surgical Pseudocholinesterase Hemodynamically None High K +; MH;
(other than procedures (<60 deficiency unstable patients muscular dystrophy;
specific allergy) min); not due to histamine children; receptor up-
recommended for release regulation settings;
continuous pseudocholinesterase
infusion deficiency

Comments Not for Pain on Significant Reversal by Organ- Trivial histamine Fastest onset, most
prolonged ICU injection; easily accumulation, cholinesterase independent release; minimal reliable NMBA for
administration reversible by prone to residual inhibitors; mixture of elimination plasma rapid tracheal
(myopathy); sugammadex; block (3-OH 3 isomers (cis-cis laudanosine and intubation
reversible by elimination half- metabolite has minimal); acrylate levels
sugammadex; life prolonged in 50% activity of edrophonium for
elimination half- ICU patient; 17- pancuronium) antagonism more
life halved in desacetyl effective during deep
late pregnancy; metabolite has block
3-desacetyl 20% activity
metabolite has
60% of the
parent
compound
potency

NA: data not available; ED 95 : effective dose to achieve 95% depression of baseline muscle contraction; NMBA: neuromuscular blocking agents; RSII: rapid sequence
induction and intubation; K +: potassium; MH: malignant hyperthermia; ST: single twitch; ICU: intensive care unit.
* The data are averages obtained from published literature and do not account for other influences such as volatile anesthetics, muscle temperature, etc.

Adapted from: Brull SJ. Neuromuscular blocking agents. In: Clinical Anesthesia, 8th ed, Barash PG, Cullen BF, Stoelting RK, et al (Eds), Wolters Kluwer, Philadelphia
2017.

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Contributor Disclosures
Rocco Ricciardi, MD, MPH Nothing to disclose Graham MacKay, MBChB, FRCS, FFST, MD Nothing to disclose Girish P Joshi, MB, BS, MD,
FFARCSI Speaker's Bureau: Mallinckrodt Pharmaceuticals [pain management (intravenous acetaminophen)]; Baxter [anesthesia (desflurane)].
Consultant/Advisory Boards: Pacira Pharmaceuticals [pain management (bupivacaine); Merck [anesthesia (sugammadex)]. Martin Weiser,
MD Nothing to disclose Wenliang Chen, MD, PhD Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-
level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required
of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

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