Table 1.
Main characteristics and results of the included studies. intraop., intraoperatively; max, maximal; n, number; No., number; NS, not significant; POD, postoperative day; postop., after operation; preop., before operation; SD, standard deviation; sEMG, surface electromyography; TCI, target controlled infusion; VAS, visual analogue scale; VASr, VAS at rest; VASs, VAS on swallowing; VRS, verbal rating scale
| Reference (and year) | No. of patients, active/placebo | Study analgesics Study arm Placebo Time of administration |
Rescue analgesic, time of administration | Duration of follow-up (days) | Analgesic outcome results (study drug vs placebo) |
|---|---|---|---|---|---|
| Atef and Fawaz23 (2008) | 38/38 | Paracetamol 1 g i.v. saline i.v. Intraop., 6, 12, 18 h |
Pethidine 1 mg kg−1 i.m. if VASr>30, 0–24 h | 1 | Paracetamol reduced total dose of i.m. pethidine during 0–24 h (P<0.001), n of pethidine doses/patient 0–24 h (P<0.001) and % of patients that needed pethidine (P<0.05) Paracetamol decreased VASs and VASr at 2 and 3 h (P<0.05) |
| Salonen and colleagues24 (2009) | 39/37/38 | Paracetamol 2 g i.v. Paracetamol 1 g i.v. Saline i.v. 10 min postop. |
Oxycodone 2 mg i.v. if VASr>30 or VASs>50, 0–6 h | 6 | Proportion of patients that needed oxycodone 0–6 h NS Paracetamol 2 g reduced n of oxycodone doses/patient 0–6 h (P=0.002), paracetamol 1 g NS. Time to 1st dose of oxycodone NS. Pain intensity NS |
| Parker and colleagues25 (1986) | 44/33/33 | Ibuprofen 600 mg p.o. Acetylsalicylic acid 600 mg p.o. 30 ml syrup p.o. 0–4 times daily for 0–6 postop. days as needed |
Analgesia p.o. or i.m., dose or type unclear, hospital Paracetamol, home |
6 | Ibuprofen provided pain relief at 30 min (% of patients with pain 50% gone) (P<0.05), at 4 h ibuprofen and acetylsalicylic acid NS Analgesic consumption: ibuprofen and acetylsalicylic acid 3–4 daily, placebo less, no numerical data. Rescue analgesia: no one requested |
| Rorarius and colleagues26 (1993) | 21/21/21 | Indomethacin 50 mg i.v. Diclofenac 75 mg i.v. Saline i.v. Intraop. |
Oxycodone 3 mg i.v., 0–70 min | <1 | Indometacin reduced n of oxycodone doses/group (P=0.05). Time to 1st rescue analgesic NS. Proportion of patients that needed oxycodone NS |
| Tarkkila and Saarnivaara27 (1999) | 20/20/20/20 | Ketoprofen 100 mg i.v. Diclofenac 75 mg i.v. Ketorolac 30 mg i.v. Saline i.v. Intraop., 6, 12 h |
Oxycodone 0.05 mg kg−1 i.v., 0–2 h Oxycodone 0.1 mg kg−1 i.m., 2–24 h |
1 | All NSAIDs reduced total n of oxycodone doses/patient 0–24 h (P<0.05) Ketorolac reduced proportion of patients that requested oxycodone (P<0.05). Pain intensity NS |
| Salonen and colleagues28 (2001) | 41/40/25 | Ketoprofen 0.5 mg kg−1 i.v. bolus with ketoprofen infusion 3 mg kg−1 Saline i.v. bolus with infusion Bolus at induction (‘intra’) or in PACU (‘post’) with 24 h infusion in both |
Oxycodone 0.05 mg kg−1 i.v. if VASr≥30, 0–4 h Oxycodone 0.1 mg kg−1 i.m. if VASr≥30, 4–24 h |
1 | Proportion of patients that needed oxycodone in PACU 0–4 h NS, intra- and post-ketoprofen at ward 5–24 h reduced (P=0.002), 0–24 h NS Intra- and post-ketoprofen reduced n of oxycodone doses/patient at all time intervals vs placebo: 0–4 h (P=0.03, P=0.04, respectively), 5–24 h (P<0.01, P<0.01, respectively) and 0–24 h (P<0.01, P<0.01 respectively). Total dose of oxycodone NS |
| Naesh and colleagues29 (2005) | 20/20 | Rofecoxib 50 mg p.o. identical capsules p.o. 1.5 h preop. |
Morphine 2.5 mg i.v. until VAS<3 or patient comfortable, 0–24 h | 1 | VAS 0–24 h NS. Rofecoxib reduced strong pain (VAS>5) 0–8 h: (P=0.02) Rofecoxib reduced total dose of morphine during 0–8 h (P<0.04) Time to 1st rescue dose NS |
| Ismail and Mowafi30 (2010) | 20/19 | Lornoxicam 16 mg i.v. Saline i.v. 30 min before induction |
Solpadeine plus (paracetamol, codeine, and caffeine in ratio of 500:8:30 mg, respectively) 2 Tablets p.o. every 4 h and Tramal 50 mg i.v. if needed, 0–24 h |
1 | Lornoxicam reduced VASs and VASr at 4 h (P<0.05) and VASs at 24 h (P<0.05) Lornoxicam increased time to 1st dose of paracetamol (P<0.05) Lornoxicam reduced total dose of paracetamol (in Solpadeine) 0–12 h (P<0.05) and 0–24 h (P<0.05). None needed Tramadol |
| Mowafi and colleagues31 (2011) | 20/20 | Lornoxicam 16 mg i.v. Saline i.v. 30 min before induction |
Diclofenac 50 mg p.r., 0.5–24 h | 1 | Lornoxicam reduced VRSmax (P<0.001) and VRSr at 4 and 24 h (P<0.001) and VRSs at 4 h (P<0.03), at 24 h NS Lornoxicam reduced total dose and increased time to 1st dose of diclofenac (P<0.001, P<0.001) |
| Xie and colleagues32 (2012) | 40/40 | Parecoxib 40 mg i.v. Saline i.v. Intraop.,10 h |
PACU: fentanyl 0.2 μg kg−1 i.v. at 10 min intervals if VRS≥5 (max 0.1 mg) Ward: paracetamol 0.5 g i.v. min. 6 h intervals (max 2 g daily) |
2 | Parecoxib reduced VRSs at 2 h (P<0.001), and VRSs and VRSr at all time points (P<0.001) Parecoxib reduced proportion of patients that needed paracetamol at ward (P<0.05), fentanyl at PACU NS |
| Ng and colleagues33 ( 2017) |
40/40 | Celecoxib 200 mg×2 p.o. identical placebo capsules p.o. 1–10 POD |
PACU: morphine i.v. or oxycodone 5 mg p.o. every 6 h or when needed Home: oxycodone 5 mg p.o., max 100 mg daily |
10 | Pain intensity (overall and daily) NS. Total dose of oxycodone NS. 1st pain-free day and return to normal activities NS |
| Fields and colleagues34 (1994) | 29/29 | Dexamethasone 8 mg i.v. Saline i.v. Intraop. |
Elixir: paracetamol 250 mg with codeine 7.5 mg in 5 ml p.o., 1–7 POD | 7 | Dexamethasone decreased pain intensity at 4 h (P<0.05), from 10 pm to 7th POD NS Total and daily dose of paracetamol+codeine elixir 1–10 POD NS |
| Carr and colleagues35 (1999) | 15/14 | Dexamethasone 20 mg i.v. Saline i.v. Intraop. |
PACU: morphine i.v., pethidine i.v. Ward: codeine and paracetamol p.o. Home: codeine p.o. every 4 h or if needed and paracetamol, 1–10 POD (doses unclear) |
10 | Pain intensity (>2 VAS change) NS. N of rescue analgesic dose in PACU NS Dexamethasone reduced total dose of pethidine/patient (P=0.03), but not total dose of morphine/patient. Proportion of patients that needed rescue analgesics in PACU NS. Daily doses of codeine and paracetamol 1–10 POD NS. Number of days taken off from school or work and time until tolerating normal diet NS |
| Stewart and colleagues36 (2002) | 48/52 | Dexamethasone 8 mg i.v. at induction, 2 mg p.o. at 10 pm, 2 mg p.o. twice daily for 1–4 POD, then 2 mg daily for 5–8 POD Saline i.v. and placebo tablets p.o. Intraop. and postop. |
PACU: morphine 2 mg i.v. Home: Co-codamol (paracetamol 1g with codeine 16 mg) 2 tablets p.o. every 6 h or if needed, 1–9 POD |
9 | Dexamethasone reduced pain intensity on all 1–9 POD, except on 0 and 2nd POD, P<0.05. Dexamethasone decreased proportion of patients that needed rescue analgesics (Co-codamol >8 per day) (P=0.024), and total dose of Co-codamol/day on 2–7 POD (P<0.05). Total dose of morphine in PACU unclear |
| Al-Shehri37 (2004) | 15/15 | Dexamethasone 6 mg i.v. Saline i.v. Intraop.,8, 16 h |
None | 10 | Dexamethasone reduced VAS on 1 POD (P<0.05) and on 8 POD (P<0.05). Total dose of analgesics NS. Patients in dexamethasone group reduced their analgesic intake earlier during 2nd week; at 7, 8, and 10 POD, P unclear |
| Rujirojindakul and colleagues38 (2008) | 25/25 | Dexamethasone 20 mg i.v. Saline i.v. Intraop. |
PACU: fentanyl i.v. every 10 min if VRS>5 (dose unclear) Ward: paracetamol 10 mg kg−1 p.o. every 6 h if VRS>5 or morphine 3 mg i.v. every 1 h if VRS>5 |
2 | Dexamethasone reduced VRS at 4 h (P=0.03), other times NS Time to first rescue analgesic NS. Total dose of rescue analgesics 0–48 h NS |
| Lachance and colleagues39 (2008) | 37/49 | Dexamethasone 8 mg i.v. and 8 mg p.o. on 0 POD at home, 6 mg twice on 1 POD, 4 mg twice on 2 POD; and 2 mg twice on 3 POD Placebo in similar manner, type unclear Intraop. and postop. |
Hospital: morphine 0.1 mg kg−1 i.v. (max 4 doses) Home: hydromorphone 1 mg p.o. (max 20 mg), 0–4 POD |
7 | Dexamethasone reduced VASs on 2 POD (P=0.047), other days NS Hydromorphone consumption, NS |
| Vaiman and colleagues40 (2011) | 30/30 | Dexamethasone 20 mg i.v. Saline i.v. 20 h postop. |
Not given 14–20 h (type or route unclear) | 1 | Dexamethasone decreased VASs (postdrug vs predrug), P=0.022, while placebo did not. Dexamethasone also decreased postdrug-VASs vs placebo (P<0.05) Dexamethasone decreased muscle reactions and normalised deglutition pattern (sEMG), while placebo did not (P<0.05) |
| Vaiman and colleagues41 (2011) | 30/30/30 | Dexamethasone 20 mg i.v. infusion Oxycodone 2 mg h−1 i.v. infusion (14 mg) Saline i.v. infusion 20 h postop. Oxycodone and placebo: infusion 16–23 h postop. |
After the EMG test was performed at 24 h (type or route unclear) | 1 | Oxycodone and dexamethasone decreased VASs (postdrug vs predrug) P<0.05, while placebo did not. Oxycodone decreased postdrug-VASs vs placebo (P<0.05), dexamethasone did not. Oxycodone decreased muscle reactions (sEMG), while dexamethasone and placebo did not (P<0.05). Oxycodone and dexamethasone, in case of oedema, decreased dysphagia (P<0.05) |
| Thimmasettaiah and Chandrappa42 (2012) | 25/25/25/25 | Dexamethasone 0.5 mg kg−1 i.v. saline I.V. preop. (after inserting i.v. cannula) vs intraop. vs postop. (PACU) placebo: intraop. |
PACU: Tramadol mg kg−1 i.v. if VAS>6 | 1 | Dexamethasone decreased VAS at 6 h (P<0.05), at 12 h (P<0.001), and at 24 h (P<0.001). Preop. and intraop. groups NS. Dexamethasone reduced n of tramadol doses 0–24 h (P<0.05) |
| Khafagy and Osman43 (2013) | 43/31 | Dexamethasone 0.3 mg kg−1 i.v. (max 8 mg) Saline i.v. Intraop. |
Unclear | 7 | Dexamethasone reduced VAS on 0 POD and on 4–7 POD (P<0.05). Dexamethasone reduced overall VAS during 0–7 POD (P=0.002). 1st liquid intake NS. 1st solid food intake: dexamethasone earlier vs control group (P=0.05) |
| Mikkelsen and colleagues44 (2006) | 22/27 | Gabapentin 1200 mg p.o. 1 h preop., 600 mg p.o. twice on 0 POD, 600 mg p.o. three times on 1–5 POD Placebo in similar manner, type unclear Preop. and postop. |
Morphine 2.5 mg i.v., 0–4 h Home: ketobemidone 2.5 mg p.o., 0–5 POD |
5 | VRSr and VASs 2–4 h and 1–5 POD, NS Total dose of morphine 0–4 h NS Gabapentin reduced total dose of ketobemidone 0–24 h, on following days NS |
| Jeon and colleagues45 (2009) | 32/26 | Gabapentin 600 mg p.o. on previous evening and 600 mg p.o. 1 h preop. Similar capsule p.o. Preop. |
PCA fentanyl 20 μg bolus, diclofenac 75 mg i.m., 0–2 POD | 9 | Gabapentin reduced VASs at 2 and 4 h (P=0.04, P=0.04), on following POD NS. VASr 0–7 POD NS Gabapentin reduced total dose of PCA fentanyl (P=0.002), and total dose of diclofenac on 0–2 POD at hospital (P=0.001). Patient satisfaction NS |
| Abdelmageed and colleagues46 (2010) | 30/30 | Gabapentin 1200 mg p.o. Placebo tablets, type unclear 2 h preop. |
Pethidine 1 mg kg−1 i.m. every 6 h if VAS≥3 or if needed | 1 | Gabapentin reduced VAS at all time points: 1, 3, 6, 12, 18, 24 h (P<0.001). Gabapentin decreased worst VAS (P<0.001) Gabapentin reduced total dose of pethidine 0–24 h (P<0.001) and increased time to 1st dose of pethidine (P<0.001) |
| Mathiesen and colleagues47 (2011) | 43/45 | Pregabalin 300 mg p.o. Placebo, type unclear 1 h preop. |
Morphine 2.5 mg i.v., 0–1 h ketobemidone 2.5 mg p.o., 0–24 h | 1 | Pregabalin reduced VASs at 2 and 4 h (P=0.009, P<0.003) Pregabalin also reduced VASs mean 2–24 h (P=0.009) and VASr at 4 h (P=0.03). Pregabalin reduced total dose of ketobemidone 1–4 h (P=0.003), 1–24 h NS. Total dose of morphine 0–1 h NS |
| Kawamata and colleagues48 (1998) | 12/12/12 | Dextromethorphan 45 mg p.o. Dextromethorphan 30 mg p.o. Starch tablet p.o. 1 h preop. |
Diclofenac 50 mg p.r., 0–6 POD | 7 | Dextromethorphan 45 mg decreased VASs and VASr on all 0–6 POD vs placebo (P<0.05). Dextromethorphan 30 mg decreased VASs on 0 POD and VASr on 0, 1, and 6 POD (P<0.05). Dextromethorphan 45 mg and 30 mg reduced total dose of diclofenac/patient (P<0.05, P<0.05). Dextromethorphan increased time to 1st dose of diclofenac (P<0.05) |
| Rafiei and colleagues49 (2012) | 20/20 | Dextromethorphan 45 mg p.o. Placebo tablet p.o. 1 h preop. |
Pethidine 0.5 mg kg−1 i.v. if VAS≥3 | 1 | Dextromethorphan increased pain-free time period (P=0.002), and decreased VASs 0–24 h (P=0.047), VASr NS. Dextromethorphan increased time to 1st dose of pethidine (P=0.005) and reduced total dose of pethidine/patient (P=0.005) |
| Van Elstraete and colleagues50 (2004) | 20/20 | Ketamine 0.5 mg kg−1 i.v. bolus with ketamine 2 μg kg−1 min−1 infusion saline i.v. bolus with i.v. infusion Bolus at induction with infusion until end of procedure |
PACU: Morphine 3 mg i.v. every 5 min until VAS<30 Ward: morphine 10 mg p.o. every 4 h until VASs<30 Ketoprofen 100 mg p.o. and paracetamol 500 mg p.o., 0–24 h |
1 | Total dose of morphine/patient NS. Time to 1st morphine dose at the ward NS. VASr, VASs NS |
| Vaiman and Krakovski51 (2012) | 30/30 | Oxycodone 2 mg h−1 (14 mg) i.v. infusion Saline i.v. infusion 16–23 h postop. |
Unclear | 1 | Oxycodone decreased VASs (postdrug vs predrug), P=0.03, while placebo did not. Oxycodone decreased postdrug VASs (oxycodone vs placebo, P<0.05) and muscle reactions (sEMG), P=0.03 |