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Perioperative pain: opioids
78 (877) Improved postoperative pain control following elective C-section with a single-dose, encapsulated, epidural morphine
Abstracts (879) Evaluation of a novel, encapsulated, epidural morphine for pain control after elective knee arthroplasty
B. Carvalho, E. Riley, G. Manvelian; SkyePharma, Inc., San Diego, CA This multicenter, randomized study compared an encapsulated morphine formulation for epidural injection (DepoMorphine) vs standard morphine (MS) following elective C-section under combined spinal epidural. Parturients (N⫽75) received 12-15 mg IT bupivacaine with 10 mg fentanyl, followed by a single epidural dose of either MS 5 mg or DepoMorphine 5, 10, or 15 mg after cord clamping. The primary end point was total supplemental oral or IV opioid analgesic (measured in IV morphine-mg equivalents) used through 48 hours post-dose. Pain intensity as measured by the visual analog scale at rest (VAS-R) and with activity (VAS-A) was analyzed over 48 hours (area under the curve analysis [AUC]: VAS scores [0-100 mm scale] were integrated over 48 hours). Mean (⫾SD) total supplemental opioid medication used through 48 hours was lower in the pooled DepoMorphine group (5⫹10⫹15 mg) vs MS (30⫾27 mg vs 47⫾34 mg; P⬍.05). Mean use was also lower on postoperative Day 2 with DepoMorphine 10 mg (12⫾9 mg) and 15 mg (11⫾21 mg) vs MS (20⫾12 mg; P⬍.05). Overall, mean AUC VAS-R scores were lower in the pooled DepoMorphine group vs MS (593⫾445 vs 1186⫾939; P⬍.01). Mean AUC VAS-A scores were lower with higher doses of DepoMorphine (10 mg: 1235⫾775; 15 mg: 1036⫾726) than with MS (2086⫾875; P⬍.001). More DepoMorphine patients rated pain control as “very good”: 32%, 53%, and 74% in DepoMorphine 5, 10, and 15 mg groups vs 22% in the MS group (P⬍.05; DepoMorphine 10 and 15 mg vs MS). There were no significant differences in AEs across treatment groups. Most were mild to moderate in severity: most common were nausea (46%), pruritus (47%), and vomiting (18%). One DepoMorphine 15 mg patient and no MS patients experienced respiratory depression (P⫽NS). DepoMorphine is a promising single-dose, encapsulated, epidural analgesic for the management of postoperative C-section pain.
C. Hartrick, G. Martin, G. Kantor, G. Manvelian; SkyePharma, Inc., San Diego, CA Randomized, double-blind study to compare analgesic efficacy of DepoMorphine, a single-dose, encapsulated, epidurally administered morphine, with IV PCA morphine following knee arthroplasty. Before surgery, patients received epidural injection of DepoMorphine 20 mg (n⫽51), 30 mg (n⫽61), or sham epidural (IV PCA morphine group; n⫽56). DepoMorphine: Patients received IV hydromorphone at first request for pain medication; after analgesia was adequate, patients had access to a placebo PCA pump. If pain control was still inadequate, patients received: (1) increased placebo PCA; and (2) bolus IV hydromorphone injection. IV PCA morphine: Patients received IV morphine at first request for pain medication; after analgesia was adequate, patients had access to an IV PCA morphine pump. If pain control was still inadequate, patients received: (1) increased IV PCA morphine; and (2) bolus IV placebo injection. Assessments: Recalled pain intensity, postoperative opioid usage (IV morphine-mg equivalents), time to first postoperative opioid use, and safety. Mean (⫾SD) recalled pain intensity scores were lower with DepoMorphine 30 mg (32⫾19) than IV PCA morphine (39⫾19; P⬍.05). DepoMorphine patients used less supplemental opioids: mean total opioid use was 39⫾42 mg (30 mg DepoMorphine), 44⫾34 mg (20 mg DepoMorphine), and 132⫾65 mg (IV PCA morphine; P⬍.0001). DepoMorphine eliminated need for supplemental opioids in a subgroup of DepoMorphine patients at 24 hours (30 mg: 28%; 20 mg: 14%; P⬍.001 vs IV PCA morphine) and 48 hours (30 mg: 15%; 20 mg: 8%; P⬍.05 vs IV PCA morphine); all IV PCA morphine patients required supplemental opioids. Median time to first postoperative opioid use was significantly longer with DepoMorphine. The incidence of pruritus was higher in the pooled DepoMorphine (20⫹30 mg) vs IV PCA morphine (57% vs 16%; P⬍.01) group. Otherwise, opioid-related adverse event rates were similar across groups. Following knee arthroplasty, DepoMorphine provided safe, effective analgesia over 48 hours.
(878) A novel, single-dose, long-acting, epidural morphine provides up to 48 hours of pain relief after abdominal surgery
(880) Encapsulated epidural morphine provides up to 48 hours of postoperative pain relief after total hip arthroplasty
D. Gambling, T. Hughes, G. Martin, G. Manvelian; SkyePharma, Inc, San Diego, CA The aim was to evaluate analgesic efficacy and safety of DepoMorphine, an encapsulated formulation of morphine administered epidurally, for lower abdominal surgery. Before surgery, adult patients (N⫽519) received an epidural injection of standard morphine (MS) 5 mg (active comparator) or DepoMorphine 5 (dose control), 10, 15, 20, or 25 mg. Postoperative PCA fentanyl use through 48 hours was the primary efficacy end point. Additionally, pain intensity at rest (VAS-R) and with activity (VAS-A) were analyzed over 48 hours (area under the curve analysis: VAS scores [0-100 mm scale] were integrated over 48 hours). Pooled higher-dose DepoMorphine group (10-25 mg) used less mean (⫾SD) postoperative fentanyl (897⫾987 g) through 48 hours than DepoMorphine 5 mg (1213⫾1079 g) and MS 5 mg (1218⫾894 g; P⬍.05). At 48 hours, no supplemental fentanyl was required in 15% of pooled higher-dose DepoMorphine patients, 6% of DepoMorphine 5 mg patients, and 2% of MS patients (P⬍.05 pooled higher-dose DepoMorphine group vs MS). Despite lower postoperative fentanyl consumption with DepoMorphine, mean AUC VAS-R scores were significantly reduced with the three highest doses of DepoMorphine (15 mg: 892⫾686; 20 mg: 854⫾725; 25 mg: 775⫾602) vs DepoMorphine 5 mg (1125⫾798) and MS (1174⫾717, P⬍.05). Twenty and 25 mg DepoMorphine doses were also associated with lower mean AUC VAS-A scores (1667⫾954 and 1602⫾932, respectively) vs MS (1998⫾898; P⬍.05). Rates of pruritus and urinary retention were higher among DepoMorphine than MS patients (54% vs 39%, and 9% vs 3%, respectively; P⬍.05). Otherwise, AEs were similar across study groups: most common were nausea (66%), pruritus (51%), pyrexia (33%), vomiting (25%), and hypotension (22%). Respiratory depression occurred in 3% of DepoMorphine-treated patients (highest rate in the 25 mg group) and 2% of MS-treated patients (P⫽NS). DepoMorphine use resulted in significantly less PCA fentanyl use and improved pain control in the postoperative period.
E. Viscusi, G. Martin, C. Hartrick, N. Singla, G. Manvelian; Skye Pharma, San Diego, CA The aim was to evaluate the analgesic efficacy and safety of DepoMorphine, a single-dose, encapsulated formulation of morphine, for epidural administration following total hip arthroplasty. Adults (N⫽194) received epidural injection of placebo or DepoMorphine 15, 20, or 25 mg before surgery. Postoperative breakthrough pain was controlled with IV fentanyl via PCA pump. Total postoperative fentanyl consumption through 48 hours was the primary end point. Assessments included pain intensity (measured by the visual analog scale at rest [VAS-R] and with activity [VAS-A]), pain control, and safety. Mean (⫾SD) fentanyl consumption was markedly lower in the pooled (15⫹20⫹25 mg) DepoMorphine group vs the placebo group (510⫾708 mg vs 2091⫾1803 mg; P⬍.0001). DepoMorphine also delayed median time to first fentanyl use (21.3 vs 3.6 hours; P⬍.0001). Despite significantly less fentanyl use among the pooled DepoMorphine group, lower mean VAS-R scores were reported in this group compared with placebo (14⫾17 vs 17⫾17, P⬍.05). More DepoMorphine than placebo patients rated pain control as “good/very good” at 24 (90% vs 65%; P⬍.05) and 48 (83% vs 67%; P⬍.05) hours. Forty-six percent of DepoMorphine patients used no fentanyl through 24 hours (placebo, 2%); 25% used no fentanyl through 48 hours (placebo, 2%; P⬍.01). Patients ⱖ years who received DepoMorphine 15 mg used less fentanyl than younger patients who received DepoMorphine 20 mg. Vomiting and pruritus rates were higher among DepoMorphine than placebo patients (49% vs 19% and 46% vs 15%, respectively; P⬍.05). Otherwise, opioid-related AEs were similar across groups; most common were nausea (69%), pyrexia (53%), hypotension (52%), vomiting (41%), and pruritus (38%). Respiratory depression occurred in 6% of DepoMorphine 15 mg patients, 0% of DepoMorphine 20 mg patients, 5% of DepoMorphine 25 mg patients, and no placebo patients (P⫽NS). Single-dose DepoMorphine provided good postoperative pain relief for 48 hours with an acceptable safety profile.
Abstracts (879) Evaluation of a novel, encapsulated, epidural morphine for pain control after elective knee arthroplasty
B. Carvalho, E. Riley, G. Manvelian; SkyePharma, Inc., San Diego, CA This multicenter, randomized study compared an encapsulated morphine formulation for epidural injection (DepoMorphine) vs standard morphine (MS) following elective C-section under combined spinal epidural. Parturients (N⫽75) received 12-15 mg IT bupivacaine with 10 mg fentanyl, followed by a single epidural dose of either MS 5 mg or DepoMorphine 5, 10, or 15 mg after cord clamping. The primary end point was total supplemental oral or IV opioid analgesic (measured in IV morphine-mg equivalents) used through 48 hours post-dose. Pain intensity as measured by the visual analog scale at rest (VAS-R) and with activity (VAS-A) was analyzed over 48 hours (area under the curve analysis [AUC]: VAS scores [0-100 mm scale] were integrated over 48 hours). Mean (⫾SD) total supplemental opioid medication used through 48 hours was lower in the pooled DepoMorphine group (5⫹10⫹15 mg) vs MS (30⫾27 mg vs 47⫾34 mg; P⬍.05). Mean use was also lower on postoperative Day 2 with DepoMorphine 10 mg (12⫾9 mg) and 15 mg (11⫾21 mg) vs MS (20⫾12 mg; P⬍.05). Overall, mean AUC VAS-R scores were lower in the pooled DepoMorphine group vs MS (593⫾445 vs 1186⫾939; P⬍.01). Mean AUC VAS-A scores were lower with higher doses of DepoMorphine (10 mg: 1235⫾775; 15 mg: 1036⫾726) than with MS (2086⫾875; P⬍.001). More DepoMorphine patients rated pain control as “very good”: 32%, 53%, and 74% in DepoMorphine 5, 10, and 15 mg groups vs 22% in the MS group (P⬍.05; DepoMorphine 10 and 15 mg vs MS). There were no significant differences in AEs across treatment groups. Most were mild to moderate in severity: most common were nausea (46%), pruritus (47%), and vomiting (18%). One DepoMorphine 15 mg patient and no MS patients experienced respiratory depression (P⫽NS). DepoMorphine is a promising single-dose, encapsulated, epidural analgesic for the management of postoperative C-section pain.
C. Hartrick, G. Martin, G. Kantor, G. Manvelian; SkyePharma, Inc., San Diego, CA Randomized, double-blind study to compare analgesic efficacy of DepoMorphine, a single-dose, encapsulated, epidurally administered morphine, with IV PCA morphine following knee arthroplasty. Before surgery, patients received epidural injection of DepoMorphine 20 mg (n⫽51), 30 mg (n⫽61), or sham epidural (IV PCA morphine group; n⫽56). DepoMorphine: Patients received IV hydromorphone at first request for pain medication; after analgesia was adequate, patients had access to a placebo PCA pump. If pain control was still inadequate, patients received: (1) increased placebo PCA; and (2) bolus IV hydromorphone injection. IV PCA morphine: Patients received IV morphine at first request for pain medication; after analgesia was adequate, patients had access to an IV PCA morphine pump. If pain control was still inadequate, patients received: (1) increased IV PCA morphine; and (2) bolus IV placebo injection. Assessments: Recalled pain intensity, postoperative opioid usage (IV morphine-mg equivalents), time to first postoperative opioid use, and safety. Mean (⫾SD) recalled pain intensity scores were lower with DepoMorphine 30 mg (32⫾19) than IV PCA morphine (39⫾19; P⬍.05). DepoMorphine patients used less supplemental opioids: mean total opioid use was 39⫾42 mg (30 mg DepoMorphine), 44⫾34 mg (20 mg DepoMorphine), and 132⫾65 mg (IV PCA morphine; P⬍.0001). DepoMorphine eliminated need for supplemental opioids in a subgroup of DepoMorphine patients at 24 hours (30 mg: 28%; 20 mg: 14%; P⬍.001 vs IV PCA morphine) and 48 hours (30 mg: 15%; 20 mg: 8%; P⬍.05 vs IV PCA morphine); all IV PCA morphine patients required supplemental opioids. Median time to first postoperative opioid use was significantly longer with DepoMorphine. The incidence of pruritus was higher in the pooled DepoMorphine (20⫹30 mg) vs IV PCA morphine (57% vs 16%; P⬍.01) group. Otherwise, opioid-related adverse event rates were similar across groups. Following knee arthroplasty, DepoMorphine provided safe, effective analgesia over 48 hours.
(878) A novel, single-dose, long-acting, epidural morphine provides up to 48 hours of pain relief after abdominal surgery
(880) Encapsulated epidural morphine provides up to 48 hours of postoperative pain relief after total hip arthroplasty
D. Gambling, T. Hughes, G. Martin, G. Manvelian; SkyePharma, Inc, San Diego, CA The aim was to evaluate analgesic efficacy and safety of DepoMorphine, an encapsulated formulation of morphine administered epidurally, for lower abdominal surgery. Before surgery, adult patients (N⫽519) received an epidural injection of standard morphine (MS) 5 mg (active comparator) or DepoMorphine 5 (dose control), 10, 15, 20, or 25 mg. Postoperative PCA fentanyl use through 48 hours was the primary efficacy end point. Additionally, pain intensity at rest (VAS-R) and with activity (VAS-A) were analyzed over 48 hours (area under the curve analysis: VAS scores [0-100 mm scale] were integrated over 48 hours). Pooled higher-dose DepoMorphine group (10-25 mg) used less mean (⫾SD) postoperative fentanyl (897⫾987 g) through 48 hours than DepoMorphine 5 mg (1213⫾1079 g) and MS 5 mg (1218⫾894 g; P⬍.05). At 48 hours, no supplemental fentanyl was required in 15% of pooled higher-dose DepoMorphine patients, 6% of DepoMorphine 5 mg patients, and 2% of MS patients (P⬍.05 pooled higher-dose DepoMorphine group vs MS). Despite lower postoperative fentanyl consumption with DepoMorphine, mean AUC VAS-R scores were significantly reduced with the three highest doses of DepoMorphine (15 mg: 892⫾686; 20 mg: 854⫾725; 25 mg: 775⫾602) vs DepoMorphine 5 mg (1125⫾798) and MS (1174⫾717, P⬍.05). Twenty and 25 mg DepoMorphine doses were also associated with lower mean AUC VAS-A scores (1667⫾954 and 1602⫾932, respectively) vs MS (1998⫾898; P⬍.05). Rates of pruritus and urinary retention were higher among DepoMorphine than MS patients (54% vs 39%, and 9% vs 3%, respectively; P⬍.05). Otherwise, AEs were similar across study groups: most common were nausea (66%), pruritus (51%), pyrexia (33%), vomiting (25%), and hypotension (22%). Respiratory depression occurred in 3% of DepoMorphine-treated patients (highest rate in the 25 mg group) and 2% of MS-treated patients (P⫽NS). DepoMorphine use resulted in significantly less PCA fentanyl use and improved pain control in the postoperative period.
E. Viscusi, G. Martin, C. Hartrick, N. Singla, G. Manvelian; Skye Pharma, San Diego, CA The aim was to evaluate the analgesic efficacy and safety of DepoMorphine, a single-dose, encapsulated formulation of morphine, for epidural administration following total hip arthroplasty. Adults (N⫽194) received epidural injection of placebo or DepoMorphine 15, 20, or 25 mg before surgery. Postoperative breakthrough pain was controlled with IV fentanyl via PCA pump. Total postoperative fentanyl consumption through 48 hours was the primary end point. Assessments included pain intensity (measured by the visual analog scale at rest [VAS-R] and with activity [VAS-A]), pain control, and safety. Mean (⫾SD) fentanyl consumption was markedly lower in the pooled (15⫹20⫹25 mg) DepoMorphine group vs the placebo group (510⫾708 mg vs 2091⫾1803 mg; P⬍.0001). DepoMorphine also delayed median time to first fentanyl use (21.3 vs 3.6 hours; P⬍.0001). Despite significantly less fentanyl use among the pooled DepoMorphine group, lower mean VAS-R scores were reported in this group compared with placebo (14⫾17 vs 17⫾17, P⬍.05). More DepoMorphine than placebo patients rated pain control as “good/very good” at 24 (90% vs 65%; P⬍.05) and 48 (83% vs 67%; P⬍.05) hours. Forty-six percent of DepoMorphine patients used no fentanyl through 24 hours (placebo, 2%); 25% used no fentanyl through 48 hours (placebo, 2%; P⬍.01). Patients ⱖ years who received DepoMorphine 15 mg used less fentanyl than younger patients who received DepoMorphine 20 mg. Vomiting and pruritus rates were higher among DepoMorphine than placebo patients (49% vs 19% and 46% vs 15%, respectively; P⬍.05). Otherwise, opioid-related AEs were similar across groups; most common were nausea (69%), pyrexia (53%), hypotension (52%), vomiting (41%), and pruritus (38%). Respiratory depression occurred in 6% of DepoMorphine 15 mg patients, 0% of DepoMorphine 20 mg patients, 5% of DepoMorphine 25 mg patients, and no placebo patients (P⫽NS). Single-dose DepoMorphine provided good postoperative pain relief for 48 hours with an acceptable safety profile.