The Current Consideration, Approach, and Management in Postcesarean Delivery Pain Control: A Narrative Review

Table 3

Randomized controlled studies evaluating efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) for postcesarean delivery analgesia.

Author (year)	Sample size	Intrathecal opioid	Analgesic regimen	Comparison groups	Pain score	Opioid consumption	Opioid-related side effects	Conclusion
Cohen (1996) [35]	48 elective cesarean deliveries under spinal anesthesia	MO 0.1-0.2 mg	Ketorolac IV 60 and then 30 q 6 h × 3 doses	Four groups; (i) Group 1: spinal morphine 0.1 mg; (ii) Group 2: spinal morphine 0.2 mg; (iii) Group 3: spinal morphine 0.1 mg + ketorolac; (iv) Group 4: ketorolac alone	No difference in pain score among the groups	20 h meperidine consumption; (i) Group 1: 72 ± 22 mg; (ii) Group 2: 46 ± 21 mg; (iii) Group 3: 39 ± 11 mg; (iv) Group 4: 49 ± 15 mg, no statistical differences	Less pruritus in group 4	Ketorolac provides satisfactory analgesia with few side effects
Pavy (2001) [91]	44 elective cesarean deliveries under CSE	Fent 12.5 μg	Ketorolac IV 30 mg at PACU and then 120 mg drip in 24 h. In postoperative day 1, initial ketorolac 15 mg IV bolus and then 105 mg IV drip in 24 h	Two groups; (i) Group 1: ketorolac group; (ii) Group 2: placebo	(i) No difference in pain with movement at 12, 24 48, or 72 h.; (ii) Worst pain score (VAS) at 12 h, group 1 : 38 [20, 50] and group 2 : 60 [43, 73], P 0.003	First 12–24 h meperidine use in mg (median (IQR)); (i) Group 1: 105 (57, 150); (ii) Group 2: 150 (108, 226), P 0.012	The severity of pruritus, sedation, and nausea did not differ between groups.	Intravenous ketorolac produced a meperidine dose-sparing effect approximately 30% but did not significantly improve pain relief, reduce opioid-related side effects, or change patient outcomes
El-Tahan (2007) [101]	90 elective cesarean deliveries under GA	No IT opioid	Ketorolac IV 15 mg bolus 20 min before induction and then drip 7.5 mg/h	Two groups; (i) Group 1: ketorolac group; (ii) Group 2: placebo	VAS score; (i) Group 1: at rest, 2 (0–6); on movement, 5 [3–9]; (ii) Group 2: at rest, 4 [3–7]; on movement, 7 [6–10],  ≤ 0.001	Number receiving tramadol first 4 h: (i) Group1: 31.1%; (ii) Group2: 15.6%, P 0.004	The frequency and severity of sedation or N/V did not differ between groups.	Prophylactic ketorolac is safe and improves the quality of analgesia after cesarean delivery.
Khezri (2018) [102]	150 elective cesarean deliveries under spinal anesthesia	No IT opioid	Ketorolac IV 30 mg (10 min before spinal anesthesia)	Three groups; (i) Group 1: ketorolac group; (ii) Group 2: meperidine group; (iii) Group 3: placebo	Mean time to first analgesia request was significantly longer in groups 1 and 2 compared with group 3.	The 24 h analgesic consumption in groups 1 and 2 was significantly smaller than group 3 ( < 0.001). However, there were no significant differences between group 1 and 2 (P 0.41).	—	Preemptive IV meperidine and ketorolac can provide a satisfying analgesia immediately after surgery.
Lowder (2003) [93]	44 cesarean delivery patients	N/A	Ketorolac 30 mg IV postoperative period	Two groups; (i) Group 1: ketorolac group; (ii) Group 2: placebo group	Pain scores were significant different at 2,3,4,6,12, or 24 h, P 0.033	24 h MO equivalents consumption was lower in the ketorolac group.; (i) Group 1: 28.1 ± 3.35 mg; (ii) Group 2: 41.6 ± 4.25 mg, P 0.008	—	Ketorolac is efficacious in reducing postoperative pain and narcotic usage after cesarean delivery.
Alhashemi (2006) [96]	45 elective cesarean deliveries under spinal anesthesia	Fent 10 μg	Ibuprofen 400 mg oral q 6 h for 48 h; first dose 30 min before surgery	Two groups; (i) Group 1: acetaminophen 1 gm IV q 6 h + ibuprofen (ii) Group 2: acetaminophen 1 g IV q 6 h + placebo	No difference of VAS between groups, P 0.143.	No difference in MO requirement; (i) Group 1: 93 ± 33 mg; (ii) Group 2: 98 ± 37 mg, P 0.628	Incidence of pruritus was higher in group 1 (45.5% vs. 82.6%, p 0.031). No difference in the incidence of N/V.	IV acetaminophen is an alternative to oral ibuprofen as an adjunct to MO PCA after cesarean delivery.
Angle (2002) [95]	80 elective cesarean deliveries under spinal anesthesia	MO 0.2 mg + Fent 10–20 μg	Naproxen 500 mg supposition then oral 550 mg q 12 h × 6 doses. Every patient received acetaminophen 300 mg + caffeine 15 mg + codeine 30 mg, 1-2 tab, PRN 3-4 h.	Two groups; (i) Group 1: naproxen group; (ii) Group 2: placebo group	Incisional pain on sitting at 36 h.; (i) Group 1: 38.2 ± 26; (ii) Group 2: 51.4 ± 25.7, P 0.05	Opioid use over time significantly less in the naproxen group,  < 0.01	No difference in the incidence of pruritus, N/V, maternal sedation, or respiratory rates	Adding regular doses of naproxen to spinal MO leads to improved analgesia on postoperative day 1.
Sun (1992) [103]	120 elective cesarean deliveries under epidural anesthesia	Epidural MO 2 mg	Diclofenac 75 mg IM on arrival in the recovery room	Four groups; (i) Group 1: diclofenac IM + epidural saline (ii) Group 2: epidural MO 2 mg + NSS; (iii) Group 3: epidural MO 2 mg + diclofenac IM; (iv) Group 4: epidural and IM saline	Overall pain relief was better in group 3 compared with other groups ( < 0.05).	Total meperidine consumption; (i) Group 1: 2450 mg; (ii) Group 2: 400 mg; (iii) Group 3: 0; (iv) Group 4: 3650 mg	Incidence of N/V and pruritus occur more frequently in groups 2 and 3 ( < 0.05).	Combined epidural MO 2 mg and diclofenac IM enhances analgesic efficacy in the treatment of both wound pain and uterine cramps
Bush (1992) [104]	50 elective cesarean deliveries under GA	—	Diclofenac IM 75 mg single dose before discontinuing anesthesia	Two groups; (i) Group1: diclofenac group; (ii) Group2: placebo group	Linear analogue scores (LAS) for pain were significantly lower in group 1 at 6 h after surgery.; (i) Group 1: 0.5 (0.2–2.0); (ii) Group 2: 2.0 (0.1–3.5),  < 0.05. However, no difference in LAS at 12 h	Cumulative papaveretum consumption at 18 h was lower in patient who received diclofenac.; (i) Group 1: 61.4 ± 30.2 mg; (ii) Group 2: 91.4 ± 23.4 mg,  < 0.05	No difference in the incidence of sedation scores or N/V by 12 h	Giving diclofenac enhances their effectiveness as analgesics.
Olofsson (1999) [99]	50 elective cesarean deliveries under spinal anesthesia	No IT opioids	Diclofenac 50 mg rectal × 3 doses in 24 h	Two groups; (i) Group 1: diclofenac group; (ii) Group 2: placebo group	VAS score during first 3 h postoperative was lower in group 1 than group 2, P 0.025	Total delivered doses of ketobemidone; (i) Group 1: 30.9 ± 3.3 mg; (ii) Group 2: 47.6 ± 3.08 mg,  < 0.01	N/A	Adding diclofenac during first 24 h reduces the need for opioids with the improved analgesic effect.
Dahl (2002) [98]	82 elective cesarean deliveries under spinal anesthesia	N/A	Diclofenac 100 mg rectal q 12 h	Two groups; (i) Group 1: diclofenac group; (ii) Group 2: placebo group	No difference in VAS	Accumulative 32 h MO consumption was less in the diclofenac group; (i) Group 1: 14 ± 1.5 mg; (ii) Group 2: 21.5 ± 1.6 mg,  < 0.05	Incidence of N/V during first 8 h was higher in the placebo group.; (i) Group 1: 0%; (ii) Group 2: 11.9%	Diclofenac suppositories 100 mg given twice daily after cesarean section are opioids sparing.
Wilder-Smith (2003) [105]	120 elective cesarean deliveries under spinal anesthesia	No IT opioid	Diclofenac 75 mg IM	Four groups; (i) Group 1: diclofenac 75 mg IM; (ii) Group 2: tramadol 100 mg IM; (iii) Group 3: diclofenac 75 mg + tramadol 100 mg IM; (iv) Group 4: placebo	Lower pain intensity ratings at rest when comparing group 3 with group 1 (at 30 min, 6 h, and 7 h postinjection;  < 0.04) and group 4 (at 30 and 60 min and 6 and 7 h;  < 0.05).	The total rescue morphine; (i) Group 1: 31 (95% CI 26–36) mg; (ii) Group 2: 35 (95% CI 32–38) mg; (iii) Group 3: 28 (95% CI 24–33) mg; (iv) Group 4: 38 (95% CI 35–41) mg,  < 0.005	No difference in the incidence of N/V or sedation score in all groups	The combination of tramadol and diclofenac resulted in improved analgesia compared with monotherapy
Bourlert (2005) [106]	64 cesarean deliveries	N/A	Diclofenac 75 mg IM single dose	Two groups; (i) Group 1: diclofenac group; (ii) Group 2: placebo group	No difference of VAS score at 1, 2, 6, and 20 h	Mean use of MO was less in the diclofenac group; Group 1: 21.69 ± 9.78 mg; Group 2: 27.4 ± 11.09 mg, P 0.016	N/A	A single dose of diclofenac IM decreases the use of morphine during the postcesarean delivery
Thienthong (2012) [107]	30 elective cesarean deliveries	MO 0.2 mg	Diclofenac 75 mg IV drip at 12 h after surgery	2 groups; (i) Group 1: diclofenac group; (ii) Group 2: placebo group	24 h mean pain score was not statistical difference	No difference in postoperative tramadol consumption between groups	No difference in incidence of N/V or abdominal discomfort	Intramuscular diclofenac 75 mg for IV route in combination with spinal MO 0.2 mg provides good analgesia within 24 h after cesarean delivery
Matsota (2013) [97]	64 elective cesarean deliveries under CSE	Fent 200 μg	Celecoxib 200 mg oral OD every patient received PCEA 0.15% ropivacaine + fent 2 mcg/ml bolus 4 ml with lockout period 15 min	2 groups; (i) Group 1: celecoxib group; (ii) Group 2: control group	The VAS scores at rest and movement were constantly lower in group 1.	No difference in the attempted doses or the total volume of the local anesthetic administration between two groups.	No difference in incidence of dizziness, sleepiness, bladder dysfunction, itching, or vomiting between the 2 groups.	A single dose of 200 mg of celecoxib effectively improved pain management in parturient with PCEA.
Inthigood (2017) [94]	82 elective cesarean deliveries under spinal anesthesia	MO 0.2 mg	Parecoxib 40 mg IV single dose	Two groups; (i) Group 1: parecoxib group; (ii) Group 2: placebo group	The VAS scores at rest were lower in the parecoxib group.; Median VAS (IQR); (i) Group 1: 1 (0, 2); (ii) Group 2: 2 (0.5, 3), P 0.01	Total meperidine consumption was no statistically difference.; (i) Group 1: 8.3 ± 16.7; (ii) Group 2: 12.7 ± 18.8, P 0.27	No patients in either group reported adverse effects from their assigned intervention	Parecoxib did not demonstrate effectiveness in reducing patient requirement for supplementary meperidine after cesarean delivery. However, administration of a single 40 mg dose of IV parecoxib after elective cesarean delivery demonstrated effectiveness in reducing pain scores

All analgesics are administered postoperatively unless indicated. All visual analogue scale or postoperative morphine consumption are reported as mean ± standard deviation (SD) unless otherwise specified. CSE, combined spinal epidural anesthesia; Fent, fentanyl; GA, general anesthesia; h, hour; IM, intramuscular; IQR, interquartile range; IT, intrathecal; IV, intravenous; min, minute; MO, morphine; N/A, not applicable; N/V, nausea and vomiting; PACU, postanesthesia care unit; PCA, patient-controlled analgesia; PCEA, patient-controlled epidural analgesia; VAS, visual analogue scale.