Summed Pain Intensity Difference Scores Research Articles

Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration < 7 days) who were deemed by their treating physician to require IV opioids. The three study groups were: 1) morphine and normal saline placebo (standard care group), 2) morphine and 0.15 mg/kg ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p < 0.02). The SPIDs for the ketamine groups were similar (p < 0.46). When compared to standard care, group 2 sustained the reduction in pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20% (p = 0.48). Among those receiving rescue analgesia, those in the standard care group received analgesia sooner than either low-dose ketamine group, on average. More participants in the low-dose ketamine groups reported dysphoria and dizziness. Low-dose ketamine is a viable analgesic adjunct to morphine for the treatment of moderate to severe acute pain. Dosing of 0.3 mg/kg is possibly more effective than 0.15 mg/kg, but may be associated with minor adverse events. Future studies should evaluate additional outcomes, optimum dosing, and use in specific populations.

Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain

ObjectiveWe assessed the analgesic effect and feasibility of low-dose ketamine combined with a reduced dose of hydromorphone for emergency department (ED) patients with severe pain. MethodsThis was a prospective observational study of adult patients with severe pain at an urban public hospital. We administered 0.5 mg of intravenous (IV) hydromorphone and 15 mg of IV ketamine, followed by optional 1 mg hydromorphone IV at 15 and 30 minutes. Pain intensity was assessed at 12 intervals over 120 minutes using a 10-point verbal numerical rating scale (NRS). Patients were monitored throughout for adverse events. Dissociative side effects were assessed using the side effects rating scale for dissociative anesthetics. ResultsOf 30 prospectively enrolled patients with severe pain (initial mean NRS, 9), 14 reported complete pain relief (NRS, 0) at 5 minutes; the mean reduction in NRS pain score was 6.0 (SD, 3.2). At 15 minutes, the mean reduction in NRS pain score was 5.0 (SD, 2.8). The summed pain intensity difference and percent summed pain intensity difference scores were 25 (95% confidence interval [CI], 21-30) and 58% (95% CI, 49-68) at 30 minutes and 41 (95% CI, 34-48) and 50% (95% CI, 42-58) at 60 minutes, respectively. Most patients (80%) reported only weak or modest side effects. Ninety percent of patients reported that they would have the medications again. No significant adverse events occurred. ConclusionsLow-dose ketamine combined with a reduced dose hydromorphone protocol produced rapid, profound pain relief without significant side effects in a diverse cohort of ED patients with acute pain.

Intranasal ketorolac for acute postoperative pain

Background:Efficacy and tolerability of intranasal ketorolac (SPRIX®) was assessed in abdominal surgery patients.Methods:Adult patients were randomly assigned to receive ketorolac 31.5 mg (n = 214) or placebo (n = 107) every 6 hr after surgery for 48 hr, then up to 4 times/day for up to 5 days. Morphine sulfate via patient controlled analgesia was available in both groups as needed.Results:Least square mean 6 hr summed pain intensity difference scores were significantly greater in the ketorolac group indicating better analgesic efficacy compared to placebo (117.4 vs. 89.9, p = 0.032; difference 27.6, 95% CI 2.5–52.7). Pain intensity difference indicated significantly better pain relief in the ketorolac group at 20 min after the first dose (p = 0.01). Morphine use over 48 hr decreased 26% in the ketorolac group compared to placebo (p = 0.004). Day 1 global pain control scores were significantly higher in the ketorolac group compared to placebo (p = 0.009). Quality of analgesia was rated significantly higher (p = 0.009) in the ketorolac group by 20 min after first dose. Adverse event and serious adverse event incidences were similar in both groups. Rhinalgia and nasal irritation, generally mild and transient in nature, occurred more frequently in the ketorolac group.Conclusion:Intranasal ketorolac was well tolerated and provided effective pain relief within 20 minutes with reduced opioid analgesia use. While IN ketorolac was assessed in an inpatient, conventional surgery setting in this study, IN ketorolac use may have more relevance for use in outpatient settings and ambulatory surgery or fast-track surgical procedures.

Analgesic effects of intranasal butorphanol tartrate administered via a unit-dose device in the dental impaction pain model: A randomized, double-blind, placebo-controlled, parallel-group study

Background: Butorphanol tartrate (BT) nasal spray is currently marketed as a multidose spray pump product. However, access to excessive amounts of drug in a single bottle (up to 15 doses) creates the potential for misuse, diversion, and abuse. Objective: This study evaluated the efficacy and tolerability of a sterile, unpreserved BT nasal spray administered via a unit-dose device in the treatment of moderate to severe pain after dental impaction surgery. Methods: This was a single-site, single-dose, randomized, double-blind, placebo-controlled, parallel-group pilot study of unit-dose BT nasal spray 1 and 2 mg compared with vehicle in patients who received standard anesthesia and underwent surgery to remove impacted third molars. When patients reported experiencing moderate or severe postoperative pain, they were assigned to receive the respective treatments in a 2:2:1 ratio. Patients rated pain intensity and pain relief and performed other assessments of analgesic efficacy before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, 4, and 6 hours after receipt of study medication. They could request rescue medication from 1 hour after the administration of nasal spray. The primary efficacy variables were summed pain intensity difference (SPID) at 2, 4, and 6 hours after administration of study medication and total pain relief at 6 hours (TOTPAR-6). Vital signs, pulse oximetry, and adverse events were monitored on the same schedule as pain assessments. Results: Thirty men and 30 women were enrolled (mean [SD] age, 22.5 [3.8] years; mean body weight, 168 [41.3] lb) and completed the trial. Pain relief was recorded in most patients within 15 minutes of receiving active treatment. A dose response was observed in SPID scores, with the 2-mg dose of BT providing the greatest response compared with placebo ( P < 0.05). Overall, 52 (86.7%) patients requested rescue medication: 22 of 24 (91.7%) in the 1-mg group, 19 of 24 (79.2%) in the 2-mg group, and 11 of 12 (91.7%) in the placebo group. The time to use of rescue medication occurred a median of 75 to 110 minutes after nasal spray dosing. The analysis of TOTPAR-6 showed no significant differences overall or in pairwise comparisons. On the global assessment, 58.3% of patients in each of the active-treatment groups and 83.3% of patients in the placebo group evaluated the study drug as “poor.” The unit-dose BT nasal spray was well tolerated, with central nervous system adverse effects being most common in the active-treatment groups compared with placebo ( P = 0.029). Dizziness occurred in 11 (45.8%) patients who received BT 1 mg, 14 (58.3%) who received BT 2 mg, and 4 (33.3%) who received placebo; for headache, the corresponding numbers were 11 (45.8%), 7 (29.2%), and 2 (16.7%). There were no significant changes from baseline in vital signs, pulse oximetry, reported nasal irritation, or pathology (eg, irritation, epistaxis, ulceration). Conclusions: In this small pilot study, sterile BT nasal spray administered via a unit-dose device provided effective postsurgical analgesia in approximately half of patients who had undergone surgery to remove impacted third molars. The results are similar to those of previous studies of BT nasal spray administered via multidose pump for postsurgical analgesia in the dental impaction pain model. The outcomes of this study are limited to the population studied.

Double-masked, single-dose comparison of bromfenac sodium, acetaminophen plus oxycodone, and placebo after oral surgery

In this double-masked, parallel-group study, patients with moderate or severe pain after surgical removal of one or more impacted third molars were randomly assigned to receive a single dose of bromfenac 25 mg or 50 mg, acetaminophen 650 mg plus oxycodone 10 mg (APOX), or placebo. Patients reported their pain intensity at baseline and at regular intervals for up to 8 hours after receiving the study medication. The following efficacy measurements were collected or derived from patient assessments: hourly pain relief, peak pain relief, total pain relief (TOPAR), hourly pain intensity difference (PID), peak PID, and summed PID (SPID). Bromfenac 25 mg or 50 mg and APOX were significantly superior to placebo for each efficacy variable. The three active drug treatments were comparable up to 3 hours after administration: bromfenac 25 mg was significantly better than APOX at hour 4, and bromfenac 50 mg was superior to APOX for all hourly variables at hours 4 to 8. Mean 8-hour TOPAR and SPID scores demonstrated that bromfenac 25 mg was at least as effective as APOX, whereas bromfenac 50 mg was significantly superior to APOX. As compared with APOX or placebo, significantly more bromfenac-treated patients had global assessments of excellent or very good. Bromfenac was well-tolerated and comparable to placebo with respect to treatment-emergent study events (adverse events that either appeared or worsened after administration of the study drug). In contrast, APOX produced significantly more study events than bromfenac or placebo, including digestive events (eg, nausea or vomiting) and nervous system events (eg, dizziness or somnolence). These results demonstrate that single oral doses of bromfenac were at least as effective as APOX in providing pain relief after oral surgery. Bromfenac produced a longer duration of analgesic action than APOX, with a comparable short time to onset of action.

Comparison of Oral Ketorolac, Intramuscular Morphine, and Placebo for Treatment of Pain After Orthopedic Surgery

Using a randomized, double-blind, placebo-controlled, parallel, single-dose, single-center, 6-hour study, we compared the analgesic response and tolerability of oral ketorolac tromethamine and intramuscular morphine sulfate and placebo. The study group comprised 176 patients with moderate, severe, or very severe pain after hip or knee surgery at a teaching hospital. Patients received either 10 mg of ketorolac orally, 10 mg of morphine intramuscularly, 5 mg of morphine IM, or placebo. Patients rated pain intensity at baseline and pain intensity and pain relief at 30 minutes, 1 hour, and hourly thereafter for 6 hours. At study completion, we evaluated overall patient ratings of pain relief and occurrence of adverse events. Summed pain intensity difference scores and total pain relief scores showed the active medications to be significantly superior to placebo and not significantly different from each other. The 10-mg dose of morphine showed a small advantage over ketorolac in peak analgesic effect, but the onset of pain relief was comparable among the active agents. The incidence of adverse events among the active-treatment groups was similar, though there was a numerical trend favoring ketorolac over 10 mg of morphine. We found oral ketorolac to be an effective alternative to parenteral opioids for the treatment of pain after hip or knee surgery in patients who can tolerate oral medication.