Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of Roflumilast on (A): Phosphodiesterase 4, gene expression (B): CERB gene expression, (C): level of PKA and (D): level of BDNF in Depressed Adult Male Wistar Rats (n = 10).

a: P<0.05 versus control group, b: P<0.05 versus depressed group.</p

Effects of Roflumilast on: (A) Forced swimming test and (B) Open Field test and (C) Number of crossed squares in Depressed Adult Male Wistar Rats (n = 10).

a: P<0.05 versus control group, b: P<0,05 versus depressed group.</p

Correlations of Dopamine (DA) and findings of behavioral tests in all studied parameters.

Correlations of Dopamine (DA) and findings of behavioral tests in all studied parameters.</p

Effects of Roflumilast on hippocampal levels of: (A) IL6, (B) dopamine and (C) cortisone in Depressed Adult Male Wistar Rats (n = 10)a: P<0.05 versus control group, b: P<0.05 versus depressed group.

Effects of Roflumilast on hippocampal levels of: (A) IL6, (B) dopamine and (C) cortisone in Depressed Adult Male Wistar Rats (n = 10)a: P<0.05 versus control group, b: P<0.05 versus depressed group.</p

Fig 8 -

a. Examination of the GFAP stained sections of CA1 region of the Control group. b. Examination of the GFAP stained sections of CA1 of the Positive control group. c. Examination of the GFAP stained sections of CA1 region of the Depressed group. d. Examination of the GFAP stained sections of CA1 region of the Roflumilast-treated group.</p

Examination of the H&E stained sections of CA1 region of the Control group.

Examination of the H&E stained sections of CA1 region of the Control group.</p

Correlations of malondialdhyde (MDA) and other parameters in all studied groups: (cAMP response element-binding protein (CERB), Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), Brain derived neurotropic factor (BDNF), Dopamine (DA), Superoxide Dismutase (SOD) Phosphodiesterase-4 (PDE-4), Interleukin-6 (IL-6) and Corticosterone (CORT)).

Correlations of malondialdhyde (MDA) and other parameters in all studied groups: (cAMP response element-binding protein (CERB), Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), Brain derived neurotropic factor (BDNF), Dopamine (DA), Superoxide Dismutase (SOD) Phosphodiesterase-4 (PDE-4), Interleukin-6 (IL-6) and Corticosterone (CORT)).</p

Fig 6 -

a. Examination of the H&E stained sections of CA1 region of the Control group. b. Examination of the H&E stained sections of CA1 region of the Positive control group. c. Examination of the H&E stained sections of CA1 region of the Depressed group. d. Examination of the H&E stained sections of CA1 region of the Roflumilast-treated group.</p

Correlations of Phosphodiesterase-4 (PDE-4) and cAMP response element-binding protein (CERB), Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), Brain derived neurotropic factor (BDNF) and Interleukin-6 (IL-6).

Correlations of Phosphodiesterase-4 (PDE-4) and cAMP response element-binding protein (CERB), Protein Kinase CAMP-Activated Catalytic Subunit Alpha (PRKACA), Brain derived neurotropic factor (BDNF) and Interleukin-6 (IL-6).</p