The morphine sparing effect of ketorolac tromethamine

A randomised, double-blind study of patients after upper abdominal surgery was undertaken to assess the analgesic efficacy of ketorolac tromethamine, a new, parenteral non-steroidal anti-inflammatory agent. Postoperatively, patients received a 24-hour intramuscular infusion of either saline (n = 20), ketorolac 1.5 mg/hour (n = 21) or ketorolac 3.0 mg/hour (n = 20). Cumulative morphine requirements were measured using a patient-controlled analgesia system which delivered intravenous increments of morphine on demand. Pain was assessed by visual analogue scores. Arterial blood gas analyses were performed pre-operatively and on the first postoperative day. Patients who received low and high dose ketorolac infusions required less morphine than the control group (p less than 0.05 and p = 0.06, respectively). This was associated with significantly lower pain scores. Patients who received the higher ketorolac dose had significantly less postoperative increase in arterial carbon dioxide tensions than controls. This study suggests that ketorolac tromethamine is a useful analgesic drug with significant morphine sparing properties.     

DOUBLE-BLIND COMPARISON OF THE MORPHINE SPARING EFFECT OF CONTINUOUS AND INTERMITTENT I.M. ADMINISTRATION OF KETOROLAC

The morphine sparing effect of ketorolac 10 mg administered4-hourly by intermittent i.m. injection was compared with acontinuous i.m. infusion in a double-blind, placebo-controlledtrial in patients undergoing upper abdominal surgery. Duringthe 48-h postoperative period, each patient was provided witha patientcontrolled analgesia (PCA) system which delivered bolusdoses of morphine and administered the intermittent i.m. dosesautomatically via a computer controlled pump. In the first 24h after surgery, there was a significant reduction in morphinedemanded by both groups receiving ketorolac compared with placebo.Patients who received a continuous infusion of ketorolac afterabdominal surgery required a median dose of morphine by PCAwhich was 49% less than controls. In the second 24 h and overthe entire 48 h of the study, patients in the continuous grouprequired significantly less morphine than those in the placebogroup. The intermittent group used less than the placebo group,but this was not significant.     

A double-blind study of the speed of onset of analgesia following intramuscular administration of ketorolac tromethamine in comparison to intramuscular morphine and placebo

A double-blind, randomised, parallel group, placebo-controlled study was performed in 85 patients to compare the speed of onset of analgesia following the intramuscular administration of a single dose of 30 mg of ketorolac tromethamine, 10 mg of morphine or placebo. A new, sensitive, method was used to measure the latency of analgesia. The onset of analgesia was defined by the time taken for the pain intensity score to reach a specified percentage of the baseline value. Twenty-five percent of patients achieving a 50% reduction in baseline pain intensity score appears to be the most appropriate parameter to assess the speed of onset of analgesia of ketorolac and morphine in the postoperative setting. Paired comparison demonstrated that ketorolac had a significantly faster onset of analgesia (p = 0.03) when compared to placebo, whilst comparison of morphine to placebo analgesic latency (p = 0.06) just failed to reach significance. There was no significant difference between the analgesic onset time of ketorolac and morphine (p = 0.73). Intramuscular ketorolac and intramuscular morphine have comparable analgesic onset times in the postoperative pain context. However, the sensitive method of measuring onset of analgesia described, highlights the slow onset of analgesia when analgesics of known efficacy are given by the intramuscular route in the postoperative period. More attention should be given to the speed of onset of analgesia in future assessments of analgesics.     

A double-blind placebo-controlled comparison of a novel formulation of intravenous diclofenac and ketorolac for postoperative third molar extraction pain

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N = 51 for all groups, except N = 47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P = .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.     

Comparison of Morphine, Ketorolac, and Their Combination for Postoperative Pain: Results from a Large, Randomized, Double-blind Trial

Background: Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs (NSAIDs) and opioids. Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results. NSAIDs have an opioid-sparing effect, but the importance of this effect is unclear. Therefore, the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects.

Methods: The study was a double-blind, randomized controlled trial. The authors randomly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously. They calculated the proportion of subjects who achieved at least 50% reduction in pain intensity 30 min after analgesic administration. Further, so long as pain intensity 30 min after analgesic administration was 5 or more out of 10, patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10. The authors assessed the presence of opioid-related side effects.

Results: Five hundred patients received morphine and 503 received ketorolac. Fifty percent of patients in the morphine group achieved pain relief, compared with 31% in the ketorolac group (difference, 19%; 95% confidence interval, 13-25%). The ketorolac-morphine group required less morphine (difference, 6.5 mg; 95% confidence interval, -5.8 to -7.2) and had a lower incidence of side effects (difference, 11%; 95% confidence interval, 5-16%) than the morphine group.     

KETOROLAC TROMETAMOL FOR POSTOPERATIVE ANALGESIA AFTER ORTHOPAEDIC SURGERY

We have compared the postoperative morphine requirements andanalgesic efficacy of four doses of i.m. ketorolac 30 mg administered6-hourly with placebo in a double-blind study of patients undergoingmajor or minor orthopaedic surgery. During the 24-h postoperativestudy period which began at the end of surgery, patients wereprescribed i.m. morphine 10 mg as required 2-hourly and assessmentswere made of pain at 4 and 24 h. After major surgery, the medianmorphine consumption over 24 h was 10 mg in patients who receivedketorolac, compared with 30 mg in those who received placebo(P = 0.008). Visual analogue pain scores and verbal pain assessmentswere better than placebo at 4 h (P = 0.028 and P = 0.008, respectively),but were not statistically different between the groups at 24h. Overall assessment of pain was similar in both groups whohad undergone major surgery. In the minor surgery groups, medianmorphine consumption was 0 mg in patients who received ketorolac,compared with 10 mg in those given placebo (ns). Visual analoguepain scores at 24 h after surgery were significantly less inpatients who had received ketorolac compared with placebo (P= 0.046) and the overall assessment of pain relief was betterin the ketorolac group (P = 0.0007). Mandatory administrationof ketorolac appeared to be of benefit in both major and minororthopaedic surgery, although the principal effects were reductionin requirement for supplementary morphine for major surgeryand better overall analgesia for minor surgery.     

Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement

We assessed the analgesic efficacy of IV propacetamol and ketorolac in a double-blinded, placebo-controlled study involving patients undergoing total hip or knee replacement procedures. On the first morning after major joint replacement surgery, 164 patients experiencing moderate-to-severe pain were randomly assigned to receive an IV infusion of propacetamol (2 g), ketorolac (15 or 30 mg), or placebo (saline). Patient-controlled analgesia with morphine was made available as a "rescue" analgesic on patient's request during the 6-h postdosing evaluation period. The median time to onset of analgesia with propacetamol (8 [95% confidence interval 6,10] min) was shorter than ketorolac 15 mg (14 [7,16] min), and placebo (16 [8; not estimable] min) although the differences did not reach statistical significance. However, compared with ketorolac 30 mg, propacetamol had a shorter duration of analgesia (3.5 [2;5.4] vs 6 [3.3; not estimable] h). Analysis of pain intensity and pain relief scores demonstrated that propacetamol produced a significantly greater improvement in pain relief than saline from 45 min until 5 h after the injection. Propacetamol was not significantly different from ketorolac 15 mg and 30 mg with respect to the main analgesic efficacy variables during the 6-h assessment period. The most frequently reported adverse event with propacetamol was injection site pain (28% vs 19% for ketorolac 15 mg, 29% for ketorolac 30 mg, and 10% for placebo, respectively). In conclusion, propacetamol (2 g IV) possesses a similar analgesic efficacy to ketorolac (15 or 30 mg IV) after total hip or knee replacement surgery.     

Intraarticular patient-controlled regional anesthesia after arthroscopically assisted anterior cruciate ligament reconstruction: ropivacaine/morphine/ketorolac versus ropivacaine/morphine

Anterior cruciate ligament reconstruction (ACLR) is associated with moderate to severe postoperative pain. We compared the intraarticular analgesic effects of ropivacaine and morphine with or without ketorolac and the need for rescue IV morphine at rest and during movement in patients undergoing anterior cruciate ligament reconstruction during spinal anesthesia. Thirty-nine patients receiving intraarticular patient-controlled regional analgesia with a 10-mL bolus and a 60-min lockout interval were randomized into 3 groups: the RM group received 0.25% ropivacaine and morphine 0.2 mg/mL; the RMK group received 0.25% ropivacaine, morphine 0.2 mg/mL and ketorolac 1 mg/mL; the P group received saline. Analgesic mixtures were prepared in 100-mL bags and coded. If needed, rescue morphine 2 mg was self-administered IV with 10-min lockout intervals. Pain scores and patient satisfaction were assessed at rest and during movement. There were no significant differences among the groups in pain scores and patient satisfaction. Daily morphine consumption was significantly smaller in the RMK group (8 +/- 8 mg) compared with the RM group (23 +/- 20 mg; P = 0.002) and in both groups compared with control (46 +/- 21 mg; P < 0.001). We conclude that intraarticular patient-controlled regional analgesia provides effective pain relief after anterior cruciate ligament reconstruction. The combination of intraarticular ropivacaine, morphine, and ketorolac was superior to control or to a combination of ropivacaine and morphine. IMPLICATIONS: This study showed the feasibility and efficacy of intraarticular patient-controlled regional analgesia technique for pain relief after anterior cruciate ligament reconstruction. The combination of intraarticular ropivacaine, morphine, and ketorolac was superior to control or to a combination of ropivacaine and morphine.     

Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery

BACKGROUND: This study tested the hypothesis that an injectable cyclooxygenase (COX)-2-specific inhibitor will be at least as effective and well tolerated as a COX-nonspecific conventional nonsteroidal antiinflammatory drug (NSAID) by comparing the analgesic efficacy and tolerability of one intravenous dose of parecoxib sodium, an injectable prodrug of the novel COX-2-specific inhibitor, valdecoxib, with ketorolac and placebo in postoperative laparotomy surgery patients. Intravenous morphine, 4 mg, was studied as a positive analgesic control. METHODS: In this multicenter, double-blinded, placebo-controlled study, women experiencing moderate-to-severe pain on the first day after abdominal hysterectomy or myomectomy received one intravenous dose of parecoxib sodium, 20 or 40 mg, ketorolac, 30 mg, morphine, 4 mg, or placebo. Analgesic efficacy and tolerability were evaluated for 24 h postdose or until patients, whose pain was not adequately controlled, opted to receive rescue analgesia. RESULTS: Two hundred two patients were enrolled. All treatment groups had comparable demographics and baseline pain status. All active treatments had an equally rapid time to onset of analgesia (10-23 min). Overall, each parecoxib sodium dose and ketorolac were significantly superior to morphine and placebo for most measures of analgesic efficacy at most time points, including a significantly longer (two- to threefold) time to rescue analgesia (P 相似文献   

Preemptive analgesic effects of ketorolac in ankle fracture surgery

BACKGROUND: Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss. METHODS: The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 microg/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured. RESULTS: The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups. CONCLUSIONS: Intravenous 30 mg ketorolac appears to have preemptive analgesic effects in patients undergoing ankle fracture repair. Ketorolac administered before tourniquet inflation prevents postoperative pain being perceived as more intense than preoperative pain.     

Efficacy and Safety of Intravenous Parecoxib Sodium in Relieving Acute Postoperative Pain following Gynecologic Laparotomy Surgery

Background: This study tested the hypothesis that an injectable cyclooxygenase (COX)-2-specific inhibitor will be at least as effective and well tolerated as a COX-nonspecific conventional nonsteroidal antiinflammatory drug (NSAID) by comparing the analgesic efficacy and tolerability of one intravenous dose of parecoxib sodium, an injectable prodrug of the novel COX-2-specific inhibitor, valdecoxib, with ketorolac and placebo in postoperative laparotomy surgery patients. Intravenous morphine, 4 mg, was studied as a positive analgesic control.

Methods: In this multicenter, double-blinded, placebo-controlled study, women experiencing moderate-to-severe pain on the first day after abdominal hysterectomy or myomectomy received one intravenous dose of parecoxib sodium, 20 or 40 mg, ketorolac, 30 mg, morphine, 4 mg, or placebo. Analgesic efficacy and tolerability were evaluated for 24 h postdose or until patients, whose pain was not adequately controlled, opted to receive rescue analgesia.

Results: Two hundred two patients were enrolled. All treatment groups had comparable demographics and baseline pain status. All active treatments had an equally rapid time to onset of analgesia (10-23 min). Overall, each parecoxib sodium dose and ketorolac were significantly superior to morphine and placebo for most measures of analgesic efficacy at most time points, including a significantly longer (two- to threefold) time to rescue analgesia (P <= 0.05). All treatments were well tolerated.     

Intramuscular ketorolac following total hip replacement with spinal anaesthesia and intrathecal morphine

We have studied the analgesic and morphine sparing effect of ketorolac tromethamine in 60 patients after total hip replacement under spinal anaesthesia.
In this double blind study 30 patients received ketorolac 30 mg IM 6 hourly postoperatively and the control group received saline. Analgesia was assessed by visual analogue pain scores (VAS) and morphine consumption by patient controlled analgesia (PCA). There was a significantly ( P <0.02) lower morphine consumption in the ketorolac group (7.1 ±8.6 mg; Mean±s.d.) when compared to the saline group (14.2±13.6 mg). Although there was a trend for lower VAS on the first postoperative night this was only significant at 10 hours postoperatively and the next morning at 08:00 hr. The incidence of side effects (emetic sequelae, pruritus and headache) were similar in both groups. It is concluded that ketorolac reduces the consumption of additional morphine in conjunction with intrathecal morphine but had no effects on the side effects.     

Preemptive Analgesic Effects of Ketorolac in Ankle Fracture Surgery

Background: Preemptive analgesia has been difficult to show in human experiments. If ketorolac has preemptive effects, then there may be an advantage to administering it at the beginning of surgery despite the potential for increased blood loss.

Methods: The authors performed a randomized, double-blind, controlled trial of 48 patients scheduled for ankle fracture surgery in a county trauma hospital. Anesthesia management was standardized and included adequate opioid analgesia (5 [mu]g/kg fentanyl and 0.1 mg/kg morphine). Intravenous 30 mg ketorolac was administered to 23 patients before tourniquet inflation and to 25 patients after tourniquet inflation. Visual analog scale pain scores, morphine patient-controlled analgesia consumption, nausea-vomiting, and postoperative bleeding were measured.

Results: The 23 patients given ketorolac before tourniquet inflation had no increase in pain postoperatively compared with their preoperative baseline (P = 0.280). The 25 patients who received ketorolac minutes later after tourniquet inflation had significant increases in their postoperative pain compared with their preoperative baseline (P = 0.00116). This effect was short-lived, and by 6 h the pain score in this group was not significantly more than it was preoperatively. Intergroup comparison showed a lower visual analog scale score at 2 (P = 0.0203) and 4 h (P = 0.00549) in the preemptive group and lower nausea scores at hour 6 (P = 0.00704). There was no difference in patient-controlled analgesia consumption between groups.     

Prospective double-blind study of effect of ketorolac administration after laparoscopic urologic surgery

BACKGROUND AND PURPOSE: To decrease postoperative dependence on narcotics for analgesia, we have evaluated ketorolac as an adjunct to perioperative pain control in patients undergoing laparoscopic urologic surgery. PATIENTS AND METHODS: Sixty-five patients (34 male, 31 female) were randomized to receive either ketorolac tromethamine (15-30 mg IV q 6 h) or placebo prior to laparoscopic surgery. Patient-controlled analgesia in the form of morphine sulfate was provided. Operative factors such as the type of surgery, operative time, and estimated blood loss were recorded. Postoperative factors such as analog pain score (range 0-10), narcotic usage, and length of stay were evaluated. RESULTS: Fifty-five patients completed the study. The average pain score was 2.2 and 4.5 for the ketorolac and placebo groups, respectively (P < 0.005). The mean amounts of total morphine used were 39.2 mg (ketorolac) and 62.5 mg (placebo) (P = 0.077). The length of stay was not significantly different in the ketorolac (2.5 days) and placebo (2.6 days) groups (P = 0.74). Operative times (P = 0.21) and estimated blood loss (P = 0.60) were not significantly different in the two groups. Ketorolac did not adversely affect renal function; serum creatinine changes were not significantly different from those in the patients receiving placebo (P = 0.50). Laparoscopic pyeloplasty necessitated more narcotic analgesia than did other laparoscopic procedures (P = 0.05). CONCLUSION: Ketorolac decreases the subjective perception of pain after laparoscopic urologic surgery. It is suggested that ketorolac administration decreases the amount of narcotic usage as well. Time to resumption of oral intake and length of hospital stay were not influenced by use of ketorolac.     

Intravenous parecoxib sodium foracute pain after orthopedic knee surgery

Our objective in a randomized, multicenter, double-blind, parallel-group, placebo- and active-controlled study was to evaluate and compare the analgesic effectiveness of single intravenous (IV) doses of parecoxib sodium 20 and 40 mg, morphine 4 mg, and ketorolac 30 mg in the postsurgical orthopedic pain model. After undergoing unilateral total knee replacement surgery, 208 healthy adult patients were randomized to receive placebo or a study drug within 6 hours of discontinuation of patient-controlled analgesia on postoperative day 1. Onset of analgesia was similarly rapid with IV parecoxib sodium 40 mg, morphine, and ketorolac. Level and duration of analgesia were significantly superior with parecoxib sodium than with morphine and were similar for parecoxib sodium and ketorolac. Parecoxib sodium was safe and well tolerated. In conclusion, IV parecoxib sodium 40 mg is as effective as ketorolac 30 mg and is more effective than morphine 4 mg and therefore has potential widespread utility in acute postoperative pain management.     

Comparison of morphine, ketorolac, and their combination for postoperative pain: results from a large, randomized, double-blind trial

BACKGROUND: Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs (NSAIDs) and opioids. Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results. NSAIDs have an opioid-sparing effect, but the importance of this effect is unclear. Therefore, the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects. METHODS: The study was a double-blind, randomized controlled trial. The authors randomly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously. They calculated the proportion of subjects who achieved at least 50% reduction in pain intensity 30 min after analgesic administration. Further, so long as pain intensity 30 min after analgesic administration was 5 or more out of 10, patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10. The authors assessed the presence of opioid-related side effects. RESULTS: Five hundred patients received morphine and 503 received ketorolac. Fifty percent of patients in the morphine group achieved pain relief, compared with 31% in the ketorolac group (difference, 19%; 95% confidence interval, 13-25%). The ketorolac-morphine group required less morphine (difference, 6.5 mg; 95% confidence interval, -5.8 to -7.2) and had a lower incidence of side effects (difference, 11%; 95% confidence interval, 5-16%) than the morphine group. CONCLUSIONS: Opioids are more efficacious analgesics than NSAIDs, although historic data for these two drugs yield similar numbers needed to treat. Adding NSAIDs to the opioid treatment reduces morphine requirements and opioid-related side effects in the early postoperative period.     

Preoperative ketorolac administration has no preemptive analgesic effect for minor orthopaedic surgery

The utility of preoperative ketorolac administration to reduce the intensity and duration of postoperative pain was compared with placebo in a randomized double-blind design of 60 ASA 1–2 patients scheduled for minor orthopaedic surgery. No opioids nor local anaesthetic blocks were used during surgery. The patients received either 30 mg ketorolac IV before surgery followed by a placebo injection after surgery or the reverse. Postoperative pain intensity was assessed repeatedly for 6 h using a visual analogue scale. No differences in pain intensity were observed between the two groups except for the initial 15-min postoperative assesments in the ketorolac group. The time to first rescue morphine administration and the total morphine consumption during the 6-h observation period were similar. It is concluded that the preoperative administration of ketorolac did not provide a significant preemptive analgesic benefit with regard to postoperative pain relief and opioid dose-sparing effect.     

EFFECTS OF KETOROLAC TROMETAMOL ON RENAL FUNCTION

We have compared the renal effects of ketorolac trometamol 10mg administered 4-hourly by intermittent i.m. injection or bycontinuous i.m. infusion with placebo in a double-blind studyin 67 patients who had undergone upper abdominal surgery. Ketorolacwas supplemented during the 48-h postoperative study periodwith bolus doses of morphine delivered by a patient controlledanalgesia system. The only significant effect of ketorolac onrenal function compared with patients who received placebo wasreduced excretion of potassium. The overall changes caused bysurgery alone were of much greater magnitude. Bleeding timewas increased with ketorolac, but there were no adverse eventsrelated to this.     

Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery

We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability. IMPLICATIONS: After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.     

The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief.

STUDY OBJECTIVE: To examine the efficacy of intramuscular (IM) ketorolac used in combination with intravenous (IV) patient-controlled analgesia (PCA) morphine for postoperative pain relief following intra-abdominal gynecologic surgery. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Patient care unit at a university medical center. PATIENTS: Thirty-five healthy women undergoing intra-abdominal gynecologic surgery who requested postoperative PCA. INTERVENTIONS: Postoperatively, all patients received IV PCA morphine, with the PCA device programmed to deliver a maximum of 1 mg every 6 minutes (maximum of 30 mg over 4 hours). In addition, patients received one of three regimens: (1) IM saline every 6 hours; (2) IM ketorolac 30 mg while in the postanesthesia care unit (PACU), followed by 15 mg every 6 hours; or (3) IM ketorolac 60 mg while in the PACU, followed by 30 mg every 6 hours. MEASUREMENTS AND MAIN RESULTS: Patients were assessed at regular intervals. Visual analog scale (VAS) scores were used to assess analgesia and patient satisfaction with therapy. Data on morphine usage were obtained from the PCA device, and the frequency and severity of adverse effects were assessed for the presence or absence of side effects. Cumulative morphine dosages were lower (p less than 0.05) in both ketorolac groups at 12, 18, and 24 hours. VAS scores and the frequency of side effects did not differ significantly among groups. CONCLUSIONS: IM ketorolac significantly decreased PCA morphine requirements. The analgesic effects of the two drugs appear to be additive.