Systematic Review and Meta-analysis of Nonsteroidal Anti-inflammatory Drugs to Improve GI Recovery After Colorectal Surgery

Chapman, Stephen J.; Garner, J; Drake, Thomas M; Aldaffaa, M; Jayne, David

doi:10.1097/dcr.0000000000001281

Cited by 30 publications

(18 citation statements)

References 26 publications

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“…NSAIDs are recommended by enhanced recovery protocols to optimize pain management and to reduce opioid‐related adverse effects. They may also improve the recovery of bowel function; a recent meta‐analysis of high‐quality RCTs demonstrated that NSAIDs reduce the times to first flatus and stool by 18 and 10 h respectively. The mechanism for this is unclear, but current evidence suggests a combination of decreased μ‐receptor agonism and inhibition of COX enzymes, which reduce neuromuscular dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…These may have benefits for the recovery of gastrointestinal function. Recent meta‐analyses of RCTs demonstrated a significant pooled benefit of NSAIDs in reducing ileus after colorectal surgery. However, the use of NSAIDs in this setting is controversial owing to the risk of acute kidney injury and conflicting reports of increased anastomotic leak rates.…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Blanco‐Colino¹,

Chapman²,

Pata³

et al. 2020

Journal of British Surgery

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Background Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non‐steroidal anti‐inflammatory drugs (NSAIDs) for reducing ileus after surgery. Methods A prospective multicentre cohort study was delivered by an international, student‐ and trainee‐led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre‐specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury. Results A total of 4164 patients were included, with a median age of 68 (i.q.r. 57–75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1–3, of whom 1061 (92·0 per cent) received non‐selective cyclo‐oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P < 0·001). Conclusion NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Blanco‐Colino¹,

Chapman²,

Pata³

et al. 2020

Journal of British Surgery

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“…93 Metaanalysis of RCTs concluded that COX2 inhibitors significantly improved time to gut recovery after elective colorectal surgery 99 and that the "drugs may represent an effective and accessible intervention to improve GI recovery". 100 A key point is that, unlike the Wattchow study, 25 preoperative dosing was not included in all studies. 100 The meta-analysis also showed the drugs to be safe in terms of renal function and rates of anastomotic leak (Level 1 evidence).…”

Section: Cyclooxygenase Inhibitorsmentioning

confidence: 99%

“…100 A key point is that, unlike the Wattchow study, 25 preoperative dosing was not included in all studies. 100 The meta-analysis also showed the drugs to be safe in terms of renal function and rates of anastomotic leak (Level 1 evidence).…”

Section: Cyclooxygenase Inhibitorsmentioning

confidence: 99%

Postoperative ileus—An ongoing conundrum

Wattchow

Heitmann

Costa

et al. 2020

Neurogastroenterology Motil

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Postoperative ileus refers to an arrest of gastrointestinal motility that complicates the recovery of up to 30% of patients undergoing gastrointestinal surgery. 1,2 It is distressing to the patient and surgeon and is expensive to manage. [3][4][5][6][7] This disruption of gut motility has its origins in the handling and resection of the gut during surgery. In brief, this activates mast cells in the gut wall and triggers subsequent infiltration by leukocytes. 8,9 This inflammatory process then causes long-term sensitization of visceral afferent nerve fibers which project to the spinal cord. These activate preganglionic and then postganglionic sympathetic motor neurons which inhibit gut motility for many hours to days. 10 Currently, treatment of patients with ileus is largely supportive. Many measures have been tried to prevent ileus 7 but, in most cases, randomized controlled trials (RCTs) have shown them to be either ineffective or minimally effective. There is a gap in understanding between the short-term arrest of gut activity seen in experimental animals and the condition in humans. | WHAT IS ILEUS?Postoperative ileus, recognized and investigated for over 100 years, 11 is a common condition and major clinical problem that occurs soon after surgery. It is largely associated with gastrointestinal surgery but can also manifest from other retroperitoneal pathology such as aortic or urinary disorders. It is characterized by a transient interruption of normal gut motor activity. Usually, postoperative ileus has relatively little impact on patient recovery and hospital discharge.

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“…Parenteral formulations of ketorolac and ibuprofen are the only IV NSAIDs currently approved for postoperative pain management in the US [16]. Studies have found that ketorolac reduces opioid consumption by 25-45% and provides additional bene ts such as improving bowel function after colorectal surgery and epidural pain after cesarean delivery [17][18][19]. Intravenous ibuprofen is approved for the management of mild to moderate pain and for the management of moderate to severe pain as an adjunct to opioid analgesics [20].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis

Carter¹,

Black²,

Sharma

et al. 2020

Preprint

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BACKGROUND The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in STATA (v15.0) to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 hours postoperatively (Sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish each treatment by efficacy and safety where higher SUCRA values indicated better outcomes. Treatments were also compared by frequency of opioid-related adverse events (ORADEs) including gastrointestinal and respiratory and reduction in morphine milligram equivalents (MME). The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS Out of 2,313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). Significantly lower MME was associated with MIV for abdominal (vs acetaminophen, ibuprofen and ketorolac), bunionectomy (vs acetaminophen), hysterectomy (vs acetaminophen and ketorolac) and orthopedic procedures (vs acetaminophen and ibuprofen). Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS MIV 30mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results, as all comparisons involving MIV were indirect.

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Systematic Review and Meta-analysis of Nonsteroidal Anti-inflammatory Drugs to Improve GI Recovery After Colorectal Surgery

Cited by 30 publications

References 26 publications

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery

Postoperative ileus—An ongoing conundrum

Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis

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