Pain management in acute musculoskeletal injury: Effect of opioid vs nonopioid medications

Table 1 Participants, intervention, comparison, outcomes, study design method for selecting clinical studies for the systematic reviews

Participants	Intervention	Comparison	Outcomes	Study design
Adult patients with catastrophic orthopedic trauma	Opioid medications	Non-opioid medications	A minimum clinically important difference in pain	Randomized controlled trials and observational studies

Table 2 Characteristics of the studies included in the qualitative synthesis

Ref.	Country/year	Injury	Opioid(s)-ROA	Nonopioid(s)-ROA	Patients /study type	Outcome (minimum clinically important difference)	Evaluation time	Efficacy result	Safety results
Soave et al[8]	Italy/1983	Severe pain due to fractures	Pentazocine-IV	Indoprofen-IV	The 40/pseudo-RCT	Any reduction on VAS	The 0 minute, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours	Pain relief in Pentazocine group	No differences
Chang et al[9]	United States/2017	Acute extremity pain	OXY/APAP-PO, HYCOD/APAP-PO, COD/APAP-PO	IBP/APAP-PO	416/RCT	Reduction of 1.3 on the NRS	2 hours	No differences	ADR in opioid
Bijur et al[10]	United States/2021	Acute musculo-skeletal pain	OXY/APAP-PO, HYCOD/APAP-PO, COD/APAP-PO	IBP/APAP-PO	600/RCT	Any reduction on NRS	The 0 hour, 1 hour or 2 hours	No differences	ADR in opioid
Buccelletti et al[11]	Italy/2014	Acute musculo-skeletal traumatic pain	COD/APAP-PO	Ketorolac-PO	134/pseudo-RCT	Any reduction on NRS	The 0 minute, 30 minutes, 2 hours	Pain relief in COD/APAP group	Not available
Craig et al[12]	United Kingdom/2012	Severe traumatic limb pain	MORPH-IV	APAP-IV	55/RCT	≥ 13 mm reduction on VAS	The 0 minute, 5 minutes, 15 minutes, 30 minutes, 60 minutes	No differences	ADR in opioid
Jalili et al[13]	Iran/2016	Severe traumatic limb pain	MORPH-IV	APAP-IV	60/RCT	Any reduction on NRS	The 0 minute, 15 minutes, 30 minutes	Pain relief in APAP group	No differences
Farahmand et al[14]	Iran/2018	Severe traumatic limb pain	MORPH-IV	Lidocaine-IV	50/RCT	Reduction of 1.3 on the NRS	The 0 minute, 15 minutes, 30 minutes, 45 minutes, 60 minutes	No differences	Heart rate/respiratory rate reduction in opioid
Gurnani et al[15]	India/1996	Acute musculo-skeletal traumatic pain	MORPH-IV	KET-subcutaneous	40/RCT	Any reduction on VAS	The 0 minute, 15 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours	Pain relief in KET group	ADR in opioid
Shimonovich et al[16]	Israel/2016	Moderate-severe acute traumatic pain	MORPH-IV/MORPH-IM	KET-IN	90/RCT	≥ 15 mm reduction and max pain reduction on VAS	Time to onset in min	No differences	No differences
Tongbua et al[17]	Thailand/2022	Moderate-severe Musculo-skeletal pain	MORPH-IV	KET-IN	74/RCT	Reduction of 1.3 on the NRS	The 0 minute, 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes and 120 minutes	No differences	No differences
Kampan et al[18]	Thailand/2024	Moderate-severe Musculo-skeletal pain (≥ 65)	MORPH-IV	KET-IN	92/RCT	Reduction of 1.3 on the NRS	The 0 minute, 30 minutes	No differences	ADR in opioid
Esfahani et al[19]	Iran/2021	Severe traumatic limb pain	MORPH-IV	KET-IV	76/RCT	Any reduction on NRS	The 0 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes	No differences	ADR in KET
Le Cornec et al[20]	France/2024	Out-of-hospital traumatic pain	MORPH-IV	KET-IV	251/RCT	Reduction of 1.3 on the NRS	The 0 minute, 30 minutes	No differences	ADR in KET
Lim et al[21]	Singapore/ 2021	Out-of-hospital traumatic pain	Tramadol-IM	MTX-inhalation	369/RCT	≥ 3-point reduction in NRS	The 0 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes	Pain relief in MTX group	ADR in MTX

APAP: Acetaminophen; ADR: Adverse drug reaction; COD: Codeine; HYCOD: Hydrocodone; IBP: Ibuprofen; IN: Intranasal; KET: Ketamine; MORPH: Morphine; MTX: Methoxyflurane; NRS: Numerical rating scale; OXY: Oxycodone; RCT: Randomized controlled trial; ROA: routes of administration; PO: Per os; IV: Intravenous; VAS: Visual analogue scale.