Efficacy and kinetics of carprofen, administered preoperatively or postoperatively, for the prevention of pain in dogs undergoing ovariohysterectomy

OBJECTIVE: To determine what effect the timing of carprofen administration has on the severity of postoperative pain in dogs undergoing ovariohysterectomy and to investigate the pharmacokinetics of carprofen under these conditions. STUDY DESIGN: A prospective, randomized, double-blind, clinical trial. ANIMALS: Sixty-two adult bitches weighing between 10 and 25 kgs, undergoing elective ovariohysterectomy. METHODS: Examinations were performed for 20 hours postoperatively using subjective visual assessment scoring systems (DIVAS) and objective mechanical nociceptive threshold measurements. Forty dogs were assigned to one of three groups: (1) preoperative carprofen; (2) postoperative carprofen; and (3) no analgesics (saline injections). The dose of carprofen was 4.0 mg/kg subcutaneously. In another 22 bitches, the pharmacokinetics of carprofen given preoperatively or postoperatively at the same dose were examined. RESULTS: The dogs given carprofen preoperatively had lower pain scores than the other groups, significantly so at 2 hours postextubation (P < .01 and P < .05, Kruskal-Wallis and post hoc Dunn's). Mechanical pain thresholds measured at the distal tibia showed the development of hyperalgesia at 12 and 20 hours postextubation; this was prevented by both the preoperative (P < .05 at 12 and 20 hours, Kruskal-Wallis) and postoperative (P < .05 at 20 hours, Kruskal-Wallis) administration of carprofen. Mechanical pain threshold testing at the wound showed a significant analgesic effect of carprofen. Plasma concentrations of carprofen were not directly related to analgesia; maximum plasma concentration, the area under the curve to the last data point, and area under the first moment curve up to the last data point were all significantly higher in the dogs given carprofen postoperatively (P < .05, Mann-Whitney). CONCLUSION: Preoperative administration of carprofen has a greater analgesic effect than postoperative administration in the early postoperative period in dogs undergoing ovariohysterectomy. Plasma levels of carprofen are not related to the degree of analgesia achieved. CLINICAL RELEVANCE: Carprofen provides effective analgesia after canine ovariohysterectomy. The timing of analgesic administration is important to optimize the control of postoperative pain.     

Critical and heretical thoughts on the development of cardiology. Limits of mental and social compliance attitude of the population

100 patients with ASA risk I & II and undergoing perianal surgery were studied for anaesthetic effects and postoperative analgesia following either intrathecal pethidine or lignocaine. Saddle block was performed either with intrathecal pethidine 5% (50 mg/ml) 0.5 mg/kg or 1 ml of 5% lignocaine. Sensory and motor block postoperative analgesia, need for additional analgesia were studied. The onset of sensory and motor blockade with lignocaine was faster than pethidine. However the sensory and motor blockade lasted longer with pethidine. The duration of postoperative analgesia was 15.39 +/- 5.14 hours as against duration of postoperative analgesia with lignocaine which was 1.3 +/- 0.53 hours. Only 10% of patients in the pethidine group required intramuscular analgesic supplementation whereas 30% of patients in the lignocaine group required intramuscular analgesic supplementation.     

Comparison of pethidine, buprenorphine and ketoprofen for postoperative analgesia after ovariohysterectomy in the cat

Sixty cats which underwent an ovariohysterectomy were randomly allocated into four treatment groups. One group (controls) received no analgesics postoperatively, and the others received either a single dose of buprenorphine (0.006 mg/kg) intramuscularly, or pethidine (5 mg/kg) intramuscularly, or ketoprofen (2 mg/kg) subcutaneously. The analgesia obtained after each treatment was assessed by three measures. There were significant differences between the groups both for the requirement for intervention analgesia (P = 0.0008) and for the overall clinical assessment (P = 0.0003) with ketoprofen requiring least intervention analgesia and having the best overall clinical assessment, followed by buprenorphine then pethidine. The control group required the most intervention analgesia and had the worst overall clinical assessment. Visual analogue scale scoring for pain produced significant differences between the groups from one hour after the operation, with the cats which were given ketoprofen tending to have lower pain scores than the other groups.     

Estimating the prevalence of delayed median nerve conduction in the general population

In a double-blind, randomized, crossover study of 25 patients after abdominal aortic surgery, we compared patient-controlled analgesia (PCA) with epidural versus intravenous pethidine. All patients received continuous epidural infusions of 0.125% bupivacaine adjusted to maintain appropriate sensory levels. The 48 hour study period commenced 36 to 48 hours after surgery and covered postoperative days 2 and 3. There was a crossover in PCA mode (epidural or intravenous) after 24 hours. Plasma pethidine concentration at the end of each 24 hour period and the total 24 hour pethidine dose did not change significantly between postoperative days 2 and 3. Pethidine plasma concentration was lower after 24 hours epidural than after intravenous PCA [125 (SD 108) ng/ml versus 171 (SD 107) ng/ml, P = 0.03], although pethidine dose did not differ significantly [mean 147 (SD 124) mg/24 h]. Visual analog pain scores (VAS) did not differ significantly between postoperative days 2 and 3, or at rest between epidural and i.v. groups. However, VAS with coughing and with abdominal palpation were lower in the epidural PCA group (P = 0.05, 0.008). With a background epidural infusion of 0.125% bupivacaine, PCA with epidural pethidine provided better pain control than PCA intravenous pethidine and this was achieved at lower plasma pethidine concentrations.     

Inguinal hernia repair: a comparison between local and general anaesthesia

BACKGROUND: A comparative analysis of outcomes of inguinal hernia repair performed under local (LA) and general anaesthesia (GA) by a single surgeon using a standardized technique of anterior transversalis repair was performed. Ninety-three cases were examined, 56 of which were cases of LA hernia repair. METHODS: A retrospective analysis of the patient hospital record was performed with particular attention to intra-operative and post-operative analgesia requirements. RESULTS: An overall series complication rate of 6.5% (6/93) is reported. Only one of 56 LA patients (2%) required more than 24 h of narcotic analgesic injections compared to 11% (4/37) in the GA group (P < 0.05). The mean total postoperative parenteral narcotic requirement in the LA group was 86+/-14 mg of pethidine as compared to the GA group who had a mean total requirement of 121+/-17 mg of pethidine (P > 0.08). CONCLUSIONS: The LA infiltration technique is an effective method for inguinal hernia repair. This series demonstrates benefits in terms of length of hospital stay and a lower incidence of postoperative parenteral narcotic analgesic requirement although when post-operative parenteral narcotics were required by the LA group of patients, the difference in mean total pethidine requirement was not statistically significant.     

Expression of LECAM-1 and LFA-1 on pre-B lymphoma cells but not on preneoplastic pre-B cells in SL/KH mice

BACKGROUND AND OBJECTIVES: The efficacy of operatively administered spinal neostigmine to provide analgesia and that of different antiemetics to prevent neostigmine-related nausea and vomiting were evaluated in patients undergoing tibial or ankle reconstruction. METHODS: One hundred patients were randomized to five groups (n = 20). The intravenous antiemetic test drug (except propofol) was given as premedication in the holding room, after intravenous midazolam, 0.05 mg/kg. The subarachnoid drugs administered were 20 mg bupivacaine (0.5%) in conjunction with 100 micrograms neostigmine, except for the saline group (S group), which received bupivacaine and saline. The S group, the neostigmine group (N group), and the propofol group (P group) received saline as the intravenous test drug. The droperidol group (D group) received intravenous droperidol 0.5 mg, and the metoclopramide group (M group) received intravenous metoclopramide 10 mg. The P group had a continuous intravenous propofol infusion (2-4 mg/kg/hr), started 10 minutes after the spinal injection. Nausea, emetic episodes, and the need for analgesic (disclofenac) or antiemetic medication were recorded for the first 24 hours following surgery and scored by a 10-cm visual analog scale (VAS). RESULTS: Subarachnoid neostigmine 100 micrograms did not affect subarachnoid bupivacaine analgesia as measured by time to first rescue analgesic in most patients, but it decreased the overall 24-hour visual analog scale (VAS) scores and the need for postoperative analgesics in 24 hours (P < .001). The incidence of intraoperative nausea and vomiting was higher in the N, D, and M groups than in the S group (P < .001). Following surgery, the 3-hour VAS assessment for emesis was higher for the N, P, and M groups than for the S group (P < .05). The overall 24-hour assessment was similar among groups. CONCLUSIONS: Subarachnoid neostigmine reduced postoperative pain scores and analgesic requirements. Whether it prolonged the duration of action of diclofenac or enhanced the mechanisms involved in spinal analgesia cannot be determined from these data. Although propofol and droperidol appeared to be more effective during and after surgery, respectively, all neostigmine groups were associated with a high consumption of antiemetics.     

The effect of the addition of adrenaline to pethidine for patient-controlled epidural analgesia after caesarean section

We have investigated the addition of adrenaline to pethidine for patient-controlled epidural analgesia after elective Caesarean section. In a randomised, double-blind study, patients received patient-controlled epidural analgesia for 24 h using pethidine 5 mg.ml-1 with adrenaline 5 micrograms.ml-1 (adrenaline group, n = 40) or pethidine 5 mg.ml-1 without adrenaline (plain group, n = 38). Visual analogue scale pain scores at rest and on coughing measured 2 h, 6 h and 24 h after surgery were similar between the two groups. There was a trend towards lower mean total consumption of pethidine in the adrenaline group (231.5 mg; SD 140.5 mg) compared with the plain group (289.5 mg; SD 139.5 mg; p = 0.071). Patients in the adrenaline group had higher visual analogue scale scores for nausea at 2 h and 24 h and higher scores for pruritus at 2 h compared with the plain group. Addition of adrenaline to pethidine for patient-controlled epidural analgesia does not appear to have significant clinical advantages.     

The tuberculin skin test in BCG-vaccinated individualse]

Endoscopy was undertaken to examine the gastroduodenal mucosa of 24 healthy dogs after seven days and again after 28 days of oral non-steroidal anti-inflammatory drug (NSAID) administration. The dogs were divided into four groups. One group received ketoprofen (1 mg/kg every 24 hours), one group carprofen (2 mg/kg every 12 hours for seven days followed by 2 mg/kg every 24 hours), a third group meloxicam suspension (0.2 mg/kg every 24 hours), and the last group gelatin (one capsule every 24 hours). Serum biochemical and complete blood count parameters did not change significantly after NSAID administration. Gastroduodenal lesions were observed in 17 dogs, but in all cases these were mild to moderate. The dogs receiving gelatin or carprofen showed the fewest and the least severe lesions, although there was no statistically significant difference between the three test drugs and the control group (P < or = 0.05). None of the dogs showed any clinical signs related to the gastrointestinal lesions.     

Rectal indomethacin potentiates spinal morphine analgesia after caesarean delivery

This double-blind, randomized study was designed to evaluate the use of indomethacin (Indocid, MSD) following caesarean delivery performed under spinal anaesthesia. Thirty ASA I-II women presenting for elective caesarean were recruited. Spinal anaesthesia was performed in a standard manner using hyperbaric bupivacaine, fentanyl and morphine. At the completion of surgery, subjects were administered two rectal suppositories, followed by 12-hourly suppositories for six doses (three days). The study group received 100 mg indomethacin suppositories and controls were given placebo (Anusol). Data collected included Visual Analog Scale (VAS) pain scores at rest and with movement, VAS scores for nausea and itch, and analgesic use. Demographic data were similar in the two groups. Median time to first analgesia (TTFA) was nine hours in the control group v. 39.5 hours in the indomethacin group (P < 0.003). Additional analgesic requests throughout the postoperative period were less in women who received indomethacin: 4 v 11 (P < 0.001). Women who received indomethacin had significantly less pain on the first postoperative day, especially on movement: mean VAS 1.4 v 5.1 (P < 0.00001). There were no reported adverse neonatal or maternal effects from the use of indomethacin. Rectal indomethacin use following caesarean delivery leads to significantly improved pain relief compared with placebo. The combination of spinal morphine and rectal indomethacin leads to high-quality postoperative analgesia.     

Early endoscopic realignment as primary therapy for complete posterior urethral disruptions

Circadian changes in the interactions between L-NG-nitroarginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, and morphine-induced antinociception were investigated by the mouse hot-plate test. Both the basal pain sensitivity and morphine-induced analgesia undergo significant 24 h variations. L-NAME (40 mg/kg, i.p.) alone did not show any antinociceptive activity, but potentiated morphine-induced analgesia when combined with morphine at all injection times. In terms of percentage absolute potentiation (%AP), L-NAME dramatically augmented the analgesic effect of morphine in the late dark period at 19 hours after lights on (HALO). It is concluded that nitric oxide (NO) is involved in the modulation of the analgesic effect of morphine; thus, the L-NAME and morphine combination might be beneficial in alleviating pain.     

Intravenous regional analgesia using morphine. The effect on postoperative pain following total knee arthroplasty

BACKGROUND: We hypothesised that any peripheral action of morphine may contribute to improved postoperative analgesia. The aim of this study was to evaluate the analgesic efficacy of morphine administered preoperatively into an exsanguinated limb prior to total knee arthroplasty. METHODS: A randomised, double-blind, controlled study was performed in 50 patients having total knee arthroplasty surgery. Patients were divided into two groups. In the study group, 0.125 mg/kg morphine in 60 ml of saline was administered intravenously (iv) into the exsanguinated operative limb via a cannula in the foot. A saline intramuscular (im) injection was administered into the opposite leg. The control group received 60 ml saline iv into the operative leg and 0.125 mg/kg morphine im into the opposite leg. Pain was assessed postoperatively using a 10-point visual analogue scale and by comparing morphine requirements and demand:delivery ratios from a patient-controlled analgesic pump. RESULTS: We found no statistically significant difference between the groups in relation to any of the analgesic measures employed. CONCLUSIONS: Intravenous regional analgesia using morphine provides no analgesic advantage over the intramuscular route from 6-24 h postoperatively.     

Patient-controlled epidural analgesia after caesarean section using a disposable device

We have evaluated the use of a disposable device, the Patient Controlled Epidural Infusor, for patient-controlled epidural analgesia (PCEA) using pethidine, for pain relief in the first 24 hours after elective Caesarean section. Patients using the Patient Controlled Epidural Infusor (n = 20) were compared with a control group (n = 20) who received PCEA using a standard electronic device. Efficacy, as assessed by visual analogue scores, was comparable to that achieved in the control group. Patient and nursing satisfaction was high and similar to that in the control group. There was a low incidence of side-effects with both devices. Patients using the disposable device used less pethidine than patients using the electronic device (median (interquartile range) 181 (100-275) mg versus 238 (213-375) mg; p = 0.035). Use of this disposable device is an acceptable alternative to more expensive and bulkier electronic devices for PCEA after Caesarean section.     

Medicolegal pitfalls in the involuntary confinement of psychiatric patients in Louisiana

OBJECTIVES: Intravenous regional anesthesia (i.v.r.) is a safe, effective technique for surgery on the upper extremities, but it provides no postoperative analgesia. The aim of this study was to evaluate the analgesic efficacy of ketorolac during and after surgery with i.v.r. induced by lidocaine. PATIENTS AND METHODS: A double blind, placebo-controlled clinical trial. Twenty-six patients undergoing elective surgery on the upper extremities under i.v.r. were studied. In the anteroom of the operating theater, an anesthesiologist prepared the anesthetic solution to be administered from two syringes. One contained 3 mg/kg of 0.5% lidocaine (0.6 ml/kg). The second syringe (2 ml) contained 1 ml of 0.9% saline solution for the control group or 1 ml with 30 mg of ketorolac for the treatment group. A second anesthesiologist received the patient in the operating theater and used the syringes provided to induce the blockade. After releasing the pneumatic tourniquets we assessed the appearance of postoperative pain on a visual analog scale over the first 24 hours. The dats were compared using parametric (Student t test) and non parametric tests (Mann-Whitney U test and Fisher's exact test). RESULTS: No significant differences in the characteristics or hemodynamic parameters analyzed were found between the two groups. Nor did we find any differences in analgesia during surgery. Ten of the 13 patients (77%) in the control group required analgesia within the first two hours, whereas none of the patients in the treatment group required analgesia during that time (p < 0.0001). There were no statistically significant differences between the two groups in the total amount administered altogether, both during and after surgery. No local or systemic side effects were observed.     

Observations on the zinc protoporphyrin/heme ratio in whole blood

The aim of this study was to examine whether severity of preoperative pain intensity is related to postoperative pain and morphine consumption. Sixty consecutive patients scheduled for total hip surgery during intrathecal anesthesia were studied. Preoperative visual analog scale (VAS) scores and analgesic intake was assessed 1 day before surgery. Three groups of patients were identified: those with mild pain (n = 12, VAS score 0-4), moderate pain (n = 18, VAS score 4-7), and severe pain (n = 28, VAS score 7-10). Postoperative pain scores were recorded in the first 24 h, as was the amount of morphine delivered by the patient-controlled analgesia pump. There were no differences among the groups in VAS scores at any time. Severe preoperative pain levels correlated with significantly greater postoperative morphine intake. The mean morphine intake during the first 24 h postoperatively was 19.2 mg in the mild pain group, 21.2 mg in the moderate pain group, and 29.5 mg in the severe pain group (P < 0.05 compared with both other groups). We conclude that patients with severe preoperative pain self-medicate to achieve postoperative pain scores equivalent to those of patients with mild and moderate pain and require a greater postoperative morphine intake for adequate analgesia than patients with mild or moderate preoperative pain. IMPLICATIONS: In this study, we showed that severity of preoperative pain intensity relates to postoperative pain levels and morphine consumption. Patients scheduled for total hip surgery with severe preoperative pain require more postoperative morphine in the first 24 h.     

Restricted expression of Fc gammaRIII (CD16) in synovium and dermis: implications for tissue targeting in rheumatoid arthritis (RA)

The authors conducted a prospective randomised double-blind comparison of patient-controlled analgesia (PCA), with a combination of morphine and ketorolac versus morphine alone and ketorolac alone in the management of postoperative pain after orthopaedic surgery. Forty-two patients were randomly assigned to three groups. Group 1 was given 1 mg/ml morphine, group 2 was given 3 mg/ml ketorolac and group 3 half-doses of each. After a loading dose of 0.07 ml/kg, PCA was started at an initial setting of 1 ml per demand, with a 10-min lock-out interval and no background infusion. Pain was measured at rest and during movements for 48 h. The combination of morphine and ketorolac was more effective than morphine or ketorolac alone in relieving rest pain throughout the study. The combination was also more effective during movement than either drug alone, but only for the first 24 h. The consumption of morphine and ketorolac was significantly lower when the two drugs were administered together. The incidence of urinary retention was highest in the group given morphine alone. The combination of half-doses of morphine and ketorolac is more effective in controlling postoperative pain than either drug alone. This combination also reduces analgesic consumption and morphine-related adverse events.     

Heme oxygenase and carbon monoxide: regulatory roles in islet hormone release: a biochemical, immunohistochemical, and confocal microscopic study

Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. In both studies, the combination was significantly superior to placebo for sum of the pain intensity differences (SPID), total pain relief (TOTPAR), peak pain intensity difference (PID) and pain relief, global evaluation, and time to remedication. The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents.     

Comparison of the fatty acid compositions in intraepithelial and infiltrating lesions of the cervix: part II, free fatty acid profiles

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.     

Postoperative analgesia in herniated disk surgery. Comparative study of diclofenac , lysine acetylsalicylate, and ketorolac

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating musculoskeletal pain and are theoretically ideal for treating postoperative pain of the lumbar column. OBJECTIVES: To compare the analgesic efficacy and side effects of treatment with 3 NSAIDs (lysine acetylsalicylate, ketorolac and diclofenac) in the treatment of pain after surgery for lumbar disc hernia. PATIENTS AND METHODS: We enrolled 75 ASA I-II patients undergoing discectomy because of lumbar disc hernia; balanced general anesthesia was used in all cases. The patients were randomly distributed in 3 groups based on type of analgesia given in the immediate postoperative period. Group A received lysine acetylsalicylate (1800 mg), group B received ketorolac (30 mg) and group C received diclofenac (75 mg). The analgesics were diluted in 100 mg of saline solution and administered through a peripheral vein over 10 min. We evaluated the analgesia attained on a visual analog scale (VAS) and the physiological response to pain was assessed by monitoring changes in arterial pressure, heart rate and breathing frequency. If analgesia was insufficient 30 min after administration of the drug, 200 mg of lysine cloximate was given as a top-up. The side effects of each drug were also recorded. RESULTS: VAS evaluation showed significant reductions in pain 60 min after administration in groups A and B and after 120 min in group C. Nine patients in each group required lysine cloximate. There were no significant differences in physiological response among the 3 groups. No patient suffered major side effects. Mild side effects were reported most often in group B. CONCLUSIONS: The NSAIDs studied were inadequately for treating pain after surgery for lumbar disc hernia. Ketorolac was no better than the other analgesics studied but was associated with a higher number of mild side effects.     

The analgesic efficacy of tenoxicam versus placebo in day case laparoscopy: a randomised parallel double-blind trial

The analgesic efficacy and duration of action of tenoxicam, an injectable non-steroidal analgesic with a long elimination half-life, were studied in day case laparoscopy in a double-blind randomised prospective parallel placebo-controlled trial. Tenoxicam 20 mg or saline was given intravenously at induction of anaesthesia in 67 women undergoing day case investigative laparoscopy for infertility or abdominal pain. Outcome measures were time to first analgesia, pain levels at 2, 4 and 24 h plus postoperative analgesic consumption in hospital and at home. The study showed no statistically significant difference in any of these measures between the two groups. Tenoxicam 20 mg intravenously immediately pre-operatively cannot be recommended for day case surgery on the basis of this study.