Gene Lambert, MD, MBA, FACP

Background: The use of multimodal non-opioid analgesics is a common practice to minimize postoperative pain and opioid analgesic use. There is limited high-quality evidence to confirm the synergistic effect and safety of acetaminophen and ibuprofen in the peripostoperative setting. The Paracetamol and NSAID in combination (PANSAID) trial investigated the analgesic efficacy and safety of four multimodal analgesic regimens after total hip arthroplasty.

Study design: Multicenter, randomized, blinded trial.

Setting: A total of six hospitals in Denmark, which represented regional and large university settings.

Synopsis: A total of 559 patients who underwent total hip arthroplasty were randomized to receive one of the following oral regimens: acetaminophen (1,000 mg) and ibuprofen (400 mg), acetaminophen (1,000 mg) and placebo, ibuprofen (400 mg) and placebo, and half-strength acetaminophen (500 mg) and ibuprofen (200 mg). One of the regimens was initiated 1 hour before surgery and continued every 6 hours for a total of 4 doses on the first postoperative day. The mean age was 67 years, and half of the patients were women.

The median morphine consumption in the 24 hours after surgery was significantly lower with ­full-strength acetaminophen-ibuprofen compared with acetaminophen monotherapy (20 mg vs. 36 mg, 99.6% confidence interval, 6.5-24; P < .001), which exceeded the prespecified 10-mg threshold for a minimal clinically important difference (MCID). The difference between acetaminophen-ibuprofen and ibuprofen monotherapy (20 mg vs. 26 mg) did not exceed the MCID, and was not clinically meaningful. The ­differences in morphine consumption with full-strength acetaminophen-ibuprofen compared to half-strength acetaminophen-ibuprofen (28 mg) and ibuprofen compared to acetaminophen monotherapy were not statistically significant.

Serious adverse events, the other primary outcome, within 90 days after surgery (15% in the ibuprofen group and 11% in the acetaminophen group, relative risk, 1.44; 97.5% CI, 0.79-2.64; P = .18) did not differ between acetaminophen monotherapy and ibuprofen monotherapy. Secondary outcomes included statistically significant analgesia (lower pain scores) at rest and with mobilization at 24 hours in the acetaminophen-ibuprofen group compared to the other groups.

An interesting observation was that acetaminophen-ibuprofen did not exceed the MCID compared to ibuprofen, which suggests that ibuprofen monotherapy may be a reasonable option for early postoperative analgesia.

Bottom line: Acetaminophen-ibuprofen reduced postoperative morphine use and had improved analgesia 24 hours after total hip arthroplasty, and was not associated with an increased 3-month risk of serious adverse events.

Citation: Thybo KH et al. Effect of combination of paracetamol (acetaminophen) and ibuprofen vs. either alone on patient-controlled morphine consumption in the first 24 hours after total hip arthroplasty. The PANSAID randomized clinical trial. JAMA. 2019;321(6):562-71.

Dr. Lambert is a hospital medicine clinician and addiction medicine specialist in the division of hospital medicine at Massachusetts General Hospital.

Background: The use of multimodal non-opioid analgesics is a common practice to minimize postoperative pain and opioid analgesic use. There is limited high-quality evidence to confirm the synergistic effect and safety of acetaminophen and ibuprofen in the peripostoperative setting. The Paracetamol and NSAID in combination (PANSAID) trial investigated the analgesic efficacy and safety of four multimodal analgesic regimens after total hip arthroplasty.

Study design: Multicenter, randomized, blinded trial.

Setting: A total of six hospitals in Denmark, which represented regional and large university settings.

Synopsis: A total of 559 patients who underwent total hip arthroplasty were randomized to receive one of the following oral regimens: acetaminophen (1,000 mg) and ibuprofen (400 mg), acetaminophen (1,000 mg) and placebo, ibuprofen (400 mg) and placebo, and half-strength acetaminophen (500 mg) and ibuprofen (200 mg). One of the regimens was initiated 1 hour before surgery and continued every 6 hours for a total of 4 doses on the first postoperative day. The mean age was 67 years, and half of the patients were women.

The median morphine consumption in the 24 hours after surgery was significantly lower with ­full-strength acetaminophen-ibuprofen compared with acetaminophen monotherapy (20 mg vs. 36 mg, 99.6% confidence interval, 6.5-24; P < .001), which exceeded the prespecified 10-mg threshold for a minimal clinically important difference (MCID). The difference between acetaminophen-ibuprofen and ibuprofen monotherapy (20 mg vs. 26 mg) did not exceed the MCID, and was not clinically meaningful. The ­differences in morphine consumption with full-strength acetaminophen-ibuprofen compared to half-strength acetaminophen-ibuprofen (28 mg) and ibuprofen compared to acetaminophen monotherapy were not statistically significant.

Serious adverse events, the other primary outcome, within 90 days after surgery (15% in the ibuprofen group and 11% in the acetaminophen group, relative risk, 1.44; 97.5% CI, 0.79-2.64; P = .18) did not differ between acetaminophen monotherapy and ibuprofen monotherapy. Secondary outcomes included statistically significant analgesia (lower pain scores) at rest and with mobilization at 24 hours in the acetaminophen-ibuprofen group compared to the other groups.

An interesting observation was that acetaminophen-ibuprofen did not exceed the MCID compared to ibuprofen, which suggests that ibuprofen monotherapy may be a reasonable option for early postoperative analgesia.

Bottom line: Acetaminophen-ibuprofen reduced postoperative morphine use and had improved analgesia 24 hours after total hip arthroplasty, and was not associated with an increased 3-month risk of serious adverse events.

Citation: Thybo KH et al. Effect of combination of paracetamol (acetaminophen) and ibuprofen vs. either alone on patient-controlled morphine consumption in the first 24 hours after total hip arthroplasty. The PANSAID randomized clinical trial. JAMA. 2019;321(6):562-71.

Dr. Lambert is a hospital medicine clinician and addiction medicine specialist in the division of hospital medicine at Massachusetts General Hospital.

Background: The use of multimodal non-opioid analgesics is a common practice to minimize postoperative pain and opioid analgesic use. There is limited high-quality evidence to confirm the synergistic effect and safety of acetaminophen and ibuprofen in the peripostoperative setting. The Paracetamol and NSAID in combination (PANSAID) trial investigated the analgesic efficacy and safety of four multimodal analgesic regimens after total hip arthroplasty.

Study design: Multicenter, randomized, blinded trial.

Setting: A total of six hospitals in Denmark, which represented regional and large university settings.

Synopsis: A total of 559 patients who underwent total hip arthroplasty were randomized to receive one of the following oral regimens: acetaminophen (1,000 mg) and ibuprofen (400 mg), acetaminophen (1,000 mg) and placebo, ibuprofen (400 mg) and placebo, and half-strength acetaminophen (500 mg) and ibuprofen (200 mg). One of the regimens was initiated 1 hour before surgery and continued every 6 hours for a total of 4 doses on the first postoperative day. The mean age was 67 years, and half of the patients were women.

The median morphine consumption in the 24 hours after surgery was significantly lower with ­full-strength acetaminophen-ibuprofen compared with acetaminophen monotherapy (20 mg vs. 36 mg, 99.6% confidence interval, 6.5-24; P < .001), which exceeded the prespecified 10-mg threshold for a minimal clinically important difference (MCID). The difference between acetaminophen-ibuprofen and ibuprofen monotherapy (20 mg vs. 26 mg) did not exceed the MCID, and was not clinically meaningful. The ­differences in morphine consumption with full-strength acetaminophen-ibuprofen compared to half-strength acetaminophen-ibuprofen (28 mg) and ibuprofen compared to acetaminophen monotherapy were not statistically significant.

Serious adverse events, the other primary outcome, within 90 days after surgery (15% in the ibuprofen group and 11% in the acetaminophen group, relative risk, 1.44; 97.5% CI, 0.79-2.64; P = .18) did not differ between acetaminophen monotherapy and ibuprofen monotherapy. Secondary outcomes included statistically significant analgesia (lower pain scores) at rest and with mobilization at 24 hours in the acetaminophen-ibuprofen group compared to the other groups.

An interesting observation was that acetaminophen-ibuprofen did not exceed the MCID compared to ibuprofen, which suggests that ibuprofen monotherapy may be a reasonable option for early postoperative analgesia.

Bottom line: Acetaminophen-ibuprofen reduced postoperative morphine use and had improved analgesia 24 hours after total hip arthroplasty, and was not associated with an increased 3-month risk of serious adverse events.

Citation: Thybo KH et al. Effect of combination of paracetamol (acetaminophen) and ibuprofen vs. either alone on patient-controlled morphine consumption in the first 24 hours after total hip arthroplasty. The PANSAID randomized clinical trial. JAMA. 2019;321(6):562-71.

Dr. Lambert is a hospital medicine clinician and addiction medicine specialist in the division of hospital medicine at Massachusetts General Hospital.

Background: Federal health system programs, including TRICARE for military personnel, spent $259 million in 2013 and $746 million in 2014 for compounded analgesic medications despite a dearth of efficacy data. The purpose of this trial was to evaluate the efficacy and functional impact of this class of medications for chronic localized pain.

Study design: Randomized, double-blind, parallel trial.

Setting: Walter Reed National Military Medical Center.

Synopsis: A total of 339 patients with at least mild, chronic localized pain were allocated to three subgroups of 133 patients based on pain type; neuropathic, nociceptive, or mixed pain. The patients in the neuropathic pain arm received a compounded formulation containing 10% ketamine, 6% gabapentin, 0.2% clonidine, and 2% lidocaine; in the nociceptive pain arm, a formulation containing 10% ketoprofen, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine; and in the mixed pain arm, a formulation containing 10% ketamine, 6% gabapentin, 3% diclofenac, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine. Half of the patients in each subgroup received the compounded formulation and the other half received placebo.

The primary outcome was the average pain score at 1 month follow-up, based on self-recorded arithmetic mean pain scores in the preceding week. Secondary outcomes included mean worst pain over the past week, functional improvement (assessed by validated Short-Form 36 Health Survey scores), and satisfaction (measured on a 1 to 5 Likert scale) with the individual treatment regimen.

Patients had small improvements in average pain scores at 1 month in the compounded formulation and placebo subgroups in all pain type categories. No significant differences were noted in the average pain scores compared to baseline, functional improvement or satisfaction in the compounded formulation and placebo groups of the total cohort or in any of the subgroups.

Bottom line: Compounded topical analgesics are costly and ineffective in the treatment of all types of chronic localized pain.

Citation: Brutcher RE et al. Compounded topical pain creams to treat localized chronic pain. Ann Intern Med. 2019;170(5):309-18.

Dr. Lambert is a hospital medicine clinician and addiction medicine specialist in the division of hospital medicine at Massachusetts General Hospital.

Background: Federal health system programs, including TRICARE for military personnel, spent $259 million in 2013 and $746 million in 2014 for compounded analgesic medications despite a dearth of efficacy data. The purpose of this trial was to evaluate the efficacy and functional impact of this class of medications for chronic localized pain.

Study design: Randomized, double-blind, parallel trial.

Setting: Walter Reed National Military Medical Center.

Synopsis: A total of 339 patients with at least mild, chronic localized pain were allocated to three subgroups of 133 patients based on pain type; neuropathic, nociceptive, or mixed pain. The patients in the neuropathic pain arm received a compounded formulation containing 10% ketamine, 6% gabapentin, 0.2% clonidine, and 2% lidocaine; in the nociceptive pain arm, a formulation containing 10% ketoprofen, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine; and in the mixed pain arm, a formulation containing 10% ketamine, 6% gabapentin, 3% diclofenac, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine. Half of the patients in each subgroup received the compounded formulation and the other half received placebo.

The primary outcome was the average pain score at 1 month follow-up, based on self-recorded arithmetic mean pain scores in the preceding week. Secondary outcomes included mean worst pain over the past week, functional improvement (assessed by validated Short-Form 36 Health Survey scores), and satisfaction (measured on a 1 to 5 Likert scale) with the individual treatment regimen.

Patients had small improvements in average pain scores at 1 month in the compounded formulation and placebo subgroups in all pain type categories. No significant differences were noted in the average pain scores compared to baseline, functional improvement or satisfaction in the compounded formulation and placebo groups of the total cohort or in any of the subgroups.

Bottom line: Compounded topical analgesics are costly and ineffective in the treatment of all types of chronic localized pain.

Citation: Brutcher RE et al. Compounded topical pain creams to treat localized chronic pain. Ann Intern Med. 2019;170(5):309-18.

Dr. Lambert is a hospital medicine clinician and addiction medicine specialist in the division of hospital medicine at Massachusetts General Hospital.

Background: Federal health system programs, including TRICARE for military personnel, spent $259 million in 2013 and $746 million in 2014 for compounded analgesic medications despite a dearth of efficacy data. The purpose of this trial was to evaluate the efficacy and functional impact of this class of medications for chronic localized pain.

Study design: Randomized, double-blind, parallel trial.

Setting: Walter Reed National Military Medical Center.

Synopsis: A total of 339 patients with at least mild, chronic localized pain were allocated to three subgroups of 133 patients based on pain type; neuropathic, nociceptive, or mixed pain. The patients in the neuropathic pain arm received a compounded formulation containing 10% ketamine, 6% gabapentin, 0.2% clonidine, and 2% lidocaine; in the nociceptive pain arm, a formulation containing 10% ketoprofen, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine; and in the mixed pain arm, a formulation containing 10% ketamine, 6% gabapentin, 3% diclofenac, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine. Half of the patients in each subgroup received the compounded formulation and the other half received placebo.

The primary outcome was the average pain score at 1 month follow-up, based on self-recorded arithmetic mean pain scores in the preceding week. Secondary outcomes included mean worst pain over the past week, functional improvement (assessed by validated Short-Form 36 Health Survey scores), and satisfaction (measured on a 1 to 5 Likert scale) with the individual treatment regimen.

Patients had small improvements in average pain scores at 1 month in the compounded formulation and placebo subgroups in all pain type categories. No significant differences were noted in the average pain scores compared to baseline, functional improvement or satisfaction in the compounded formulation and placebo groups of the total cohort or in any of the subgroups.

Bottom line: Compounded topical analgesics are costly and ineffective in the treatment of all types of chronic localized pain.

Citation: Brutcher RE et al. Compounded topical pain creams to treat localized chronic pain. Ann Intern Med. 2019;170(5):309-18.

Dr. Lambert is a hospital medicine clinician and addiction medicine specialist in the division of hospital medicine at Massachusetts General Hospital.