Diamorphine-bupivacaine mixture compared with plain bupivacaine for analgesia

We have studied the efficacy of two extradural infusions (10 ml h-1) in 50 patients in active labour. Patients in the diamorphine group (n = 25) received 0.0625% plain bupivacaine 6.25 mg h-1 mixed with 0.005% diamorphine 0.5 mg h-1 and those in the control group (n = 25) received 0.125% plain bupivacaine 12.5 mg h-1. Both groups received intermittent "top-ups" of 0.25% bupivacaine 10 ml when indicated. Although median pain scores during the infusion were similar in both groups, patients in the diamorphine group indicated greater satisfaction with the infusion (88% very satisfied, compared with 52% in the control group (P < 0.02)). There were no differences in the incidence of hypotension, instrumental vaginal delivery, number of "top-ups", duration of the second stage or extent of motor block. However, patients in the diamorphine group had a high incidence of pruritus (44%, compared with 0% in the control group (P < 0.01)).     

Intrathecal sufentanil compared with epidural bupivacaine analgesia in labour

Epidural analgesia for pain relief during labour has certain disadvantages including slow onset. However, intrathecal sufentanil provides rapid onset and well-controlled analgesia lasting 1-4 h. The aim of this study was to compare the analgesia and the side effects of intrathecal sufentanil with epidural bupivacaine during labour. In a randomized, double-blind and controlled trial 58 parturient women requesting analgesia during labour were studied. The patients received either intrathecal sufentanil 10 micrograms and epidural saline, or intrathecal saline and epidural bupivacaine 20 mg. Visual analogue scores (VAS) for pain, blood pressure, heart rate, respiratory rate, level of sedation and the incidence of pruritus and nausea were recorded. Pain scores were significantly lower between 5 and 90 min after injection in patients receiving intrathecal sufentanil. Pruritus was significantly more frequent among those receiving intrathecal sufentanil. The rapid onset and effective analgesia of intrathecal sufentanil may in certain situations be advantageous.     

Continuous spinal analgesia. Comparison between patient-controlled and bolus administration of plain bupivacaine for postoperative pain relief

The purpose of this study was to examine the changing trends in surgical management of patients with abdominal aortic aneurysms at a tertiary care teaching hospital over the past 40 years, by analysis of demographic data, perioperative variables and outcomes on all patients having abdominal aortic aneurysm surgery between 1955 and 1993. Some 1604 abdominal aortic aneurysms were assessed. The annual rate of abdominal aortic aneurysm surgery increased from 17.6 to 67.8 cases per year. The non-ruptured to ruptured abdominal aortic aneurysm ratio increased from 2.4:1 in the first decade to 3.4:1 in the last 5 years. In non-ruptured abdominal aortic aneurysm repairs, the following variables changed over the four decades: patients age over 80 years increased (2.4% to 8.0%; P<0.04), concomitant lower-limb occlusive disease increased (12.2% to 23.7%; P<0.02), prevalence of smaller aneurysms (4-6 cm) increased (16.0% to 54.2%; P<0.0001); intraoperative hypotension decreased (9.0% to 0.7%; P<0.0001), postoperative hemorrhage decreased (8.2% to 0.0%, P<0.0001), postoperative leg ischemia decreased (5.7% to 1.1%; P<0.02) and postoperative amputation rate decreased (3.2% to 0.0%; P<0.03). There was a significant decrease in perioperative mortality (17.0% to 3.4%; P<0.0001). For ruptured aneurysms, early operation (within 1 h of admission) increased from 8.7% to 55.8% (P<0.0001), prevalence of intraoperative hypotension decreased (50.0% to 23.5%; P<0.001), and major venous injury decreased (18.0% to 5.2%; P<0.05). Mortality, however, did not decrease significantly (54.2% to 44.2%; P=0.32). In conclusion, there was a significant decrease in mortality and morbidity associated with non-ruptured abdominal aortic aneurysm repair over the four decades studied. In addition, older patients with smaller aneurysms and more co-morbid conditions were operated on during this period. Mortality for patients operated on for ruptured abdominal aortic aneurysm repair has not changed significantly.     

Influence of timing of administration on the analgesic effect of bupivacaine infiltration in carrageenin-injected rats

BACKGROUND: Recent evidence has suggested that the timing of administration of analgesic drugs could influence their efficacy by reducing the sensitization of the nervous system induced by the nociceptive inputs, but this concept of preemptive analgesia is still debated in both clinical and basic research. METHODS: The model of acute inflammatory pain induced by carrageenin was used to study the influence of timing of administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005 mg/ml epinephrine) on the development of hyperalgesia, edema, and increase in temperature. The animals received bupivacaine 5 min before (BUPI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrageenin (1 ml/kg of 1% solution) was injected into the left hind paw. Two control groups (n = 15 in each) received saline 5 min before or 60 min after administration of carrageenin. Hyperalgesia of the injected paw was evaluated by the vocalization threshold to paw pressure, edema by measuring paw circumference with a thread, and plantar temperature with a thermocouple thermometer. All measurements were done before carrageenin injection then every 30 min thereafter for 240 min. Another series (n = 24), with the same four groups was also evaluated at 24 h. RESULTS: Local injection of bupivacaine 60 min after carrageenin partially reduced the edema and hyperalgesia. The injection of bupivacaine 5 min before carrageenin was more efficient than the delayed injection and reduced hyperalgesia, edema and the increase in temperature temporarily, but did not totally prevent their development. All groups were similar at 240 min and 24 h. CONCLUSIONS: These results show that a slight advantage of infiltration with bupivacaine before injury exists in this carrageenin model of acute inflammatory pain. However, this benefit is limited in time and bupivacaine did not have any preemptive analgesic effect.     

Controlled systemic absorption and increased anesthetic effect of bupivacaine following epidural administration of bupivacaine-hydroxypropyl-beta-cyclodextrin complex

PURPOSE: To investigate the influence of complexation between bupivacaine and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the systemic absorption and on the pharmacodynamic effect of bupivacaine following epidural administration in a rabbit model. METHODS: Bupivacaine and bupivacaine-HP-beta-CD complex were administered according to a randomized and cross-over design in six rabbits chronically instrumented with an epidural catheter. The plasma concentrations of bupivacaine and the duration and intensity of the motor blockade were evaluated. RESULTS: Complexation with HP-beta-CD led to a decrease in the maximum plasma concentration of bupivacaine. Individual absorption kinetics evaluated by Loo-Riegelman absorption analysis indicated that systemic absorption resulted from two parallel first-order processes. Only the faster absorption phase was slowed by complexation with HP-beta-CD. The duration of the motor blockade was increased almost twice but the intensity was not modified. CONCLUSIONS: Complexation with HP-beta-CD could be a promising drug delivery system to improve the therapeutic index of bupivacaine.     

Comparison of pre- versus post-incision administration of intrathecal bupivacaine and intrathecal morphine in a rat model of postoperative pain

BACKGROUND: Preclinical studies in experimental animals suggest that preemptive analgesia may improve postoperative pain management. The beneficial effects of preemptive analgesia appear less remarkable clinically. The purpose of this study is to examine the effect of pre- and post-incision administration of intrathecal bupivacaine and intrathecal morphine in a rat model for postoperative pain. METHODS: Rats with intrathecal catheters were anesthetized with halothane, and the surgical field was prepared. A saline vehicle or the test drug was administered 15 min before an incision was made in the plantar aspect of the hindpaw or after the incision was completed. After recovery, mechanical hyperalgesia to punctate and nonpunctate stimuli was measured. Rats were tested on the day of surgery for the first 5 h and each day for 6 days. RESULTS: In saline vehicle-treated rats, the median withdrawal threshold decreased from 522 mN to 54 mN or less, and the response frequency to pressure from application of the plastic disc increased from 0 +/- 0% to 96 +/- 12% or greater after incision. Hyperalgesia was persistent through 2 days after surgery and then gradually returned toward preincision values over the next 4 days. Pre- or postincision administration of either intrathecal morphine or intrathecal bupivacaine reduced hyperalgesia on the day of surgery; at all subsequent times, there were no differences between the saline vehicle groups and the drug treatment groups. There were never any significant differences between pre- and postincision treatments. CONCLUSIONS: Early reduction in pain behaviors either by pre- or postincision management had no impact on subsequent measures of hyperalgesia in this model. These results agree with a number of clinical studies and suggest that incisional pain may be initiated and maintained differently than pain in other models.     

Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC

In recent years, the Th1/Th2 concept has become of prime importance in the understanding of heterogeneous responses of the immune system and implications thereof for infectious and autoimmune diseases. Originally established on the basis of different cytokines produced by T cell clones, it is now known that the Th1/Th2 concept really defines totally different immune pathways that affect most if not all cells of the immune system. Murine experimental leishmaniasis was the first model to confirm the relevance of the Th1/Th2 concept in vivo. Herein, we summarize the current knowledge on the characteristics and generation of Th1 and Th2 cells, as well as on recent advances of the application of this concept to murine cutaneous leishmaniasis.     

Respiratory depression following administration of intrathecal bupivacaine to an opioid-dependent patient

OBJECTIVE: To document two cases of respiratory depression in patients receiving morphine once the stimulating effect of pain on respiration was removed by bupivacaine. CASE SUMMARIES: Case 1: A 72-year-old 84-kg white man with cancer of the bladder and bone metastases had intense back and leg pain that was treated with intrathecal morphine for 6 months at an increasing dosage up to 10 mg twice daily. The intrathecal route was avoided for 4 days because of a suspected local infection at the site of the intrathecal catheter. During this 4-day period the patient received extended-release morphine and subcutaneous morphine daily. When the intrathecal route was used again, he received an identical dose of morphine plus bupivacaine and epinephrine. Ten minutes after the injection, fatal respiratory distress occurred. Case 2: A 92-year-old white woman was admitted for revascularization of arteritis on her left leg. To treat a painful sacrum and heel bedsores, she received extended-release oral morphine for 8 days. Induction of the intrathecal anesthesia was performed with bupivacaine. After 10 minutes, the patient became subcomatose, with miosis and apnea. Intravenous naloxone restored spontaneous respiration and normal consciousness. CONCLUSIONS: Pain is a physiologic antagonist of the respiratory depressant effects of opioid analgesics. By reducing pain stimulation, bupivacaine may make patients more susceptible to opioid respiratory depression. Such situations require titration of bupivacaine and other analgesics as well as increased monitoring of the patient.     

Tropisetron or ondansetron compared with placebo for prevention of postoperative nausea and vomiting

In a prospective, randomized, double-blind, placebo-controlled, multicentre study, the efficacy of prophylactic tropisetron (2 mg) or ondansetron (4 mg) for the prevention of post-operative nausea and vomiting after abdominal or non-abdominal surgery with general balanced anaesthesia was studied in 842 ASA I-III patients. In patients undergoing abdominal surgery, ondansetron and tropisetron reduced the frequency of emetic episodes compared with the placebo (29%, 30% vs. 42% respectively). In men, neither tropisetron nor ondansetron had an effect different from the placebo, whereas in women both drugs led to lower rates of emetic episodes and nausea. In comparison with abdominal surgery, fewer patients in the non-abdominal surgery subgroup had emetic episodes (42% vs. 23% in the placebo group). However, neither tropisetron nor ondansetron was significantly different from the placebo in this patient subgroup. In conclusion, for patients at increased risk of post-operative nausea and vomiting, a prophylactic therapy at the lowest effective dose with tropisetron or ondansetron may be useful.     

The peripheral effect of fentanyl on postoperative pain

The clinical value of the analgesic effect of opioids administered peripherally (except for intraarticular administration) has not been clearly demonstrated. The aim of this study was to test the hypothesis that fentanyl, added to a local anesthetic for wound infiltration, can enhance postoperative analgesia via a peripheral mechanism. Patients with inguinal herniorrhaphy performed under spinal anesthesia were randomly assigned to one of two groups (n = 10 each). At the end of surgery, the wound was infiltrated with 10 mL of lidocaine 0.5% and fentanyl 0.001% (10 microg) in one group; in the other group, the wound was infiltrated with 10 mL of lidocaine 0.5% alone (and fentanyl 10 microg IM contralaterally). The following variables were determined in a double-blind manner: the duration of anesthesia (response to a von Frey filament), the duration of analgesia (time to mild postoperative pain), postoperative meperidine consumption, intensity visual analog scale of spontaneous and movement-associated pain 24 h after surgery, and wound pain threshold 24 h after surgery (pressure algometry). The addition of fentanyl for wound infiltration enhanced the duration of anesthesia (130+/-37 vs 197+/-27 min; P < 0.001) and decreased the intensity of spontaneous (50+/-17 vs 19+/-18 mm; P < 0.002) and movement-associated (56+/-15 vs 26+/-21 mm; P < 0.002) pain 24 h postoperatively. Differences between groups for other variables were not statistically significant. Fentanyl added to a local anesthetic for wound infiltration after spinal anesthesia can enhance postoperative analgesia by a peripheral mechanism. IMPLICATIONS: Fentanyl can enhance analgesia by a peripheral mechanism. Added to a local anesthetic for wound infiltration, it may be of benefit for the relief of postoperative pain.     

Analgesia following day-case knee arthroscopy--the effect of piroxicam with or without bupivacaine infiltration

Sixty patients presenting for day-case arthroscopy of the knee under general anaesthesia were studied. Patients were randomly allocated to receive, in addition to intramuscular piroxicam 20 mg, either bupivacaine 0.25% 20 ml applied locally to the knee at the end of the procedure (n = 30) or no further intra-operative analgesia (n = 30). Visual analogue pain scores were significantly lower at 1, 2 and 4 h postoperatively in the bupivacaine group (p < 0.05). A higher proportion of patients in the piroxicam-only group required supplemental analgesia before discharge from hospital. The combination of piroxicam and bupivacaine provided superior analgesia to piroxicam alone.     

Analgesic effect of bupivacaine on extraperitoneal laparoscopic hernia repair

BACKGROUND: Occurrence of cryptococcal endophthalmitis is rare and commonly is associated with widespread disseminated diseases. The authors report here a well-documented case of endogenous cryptococcal endophthalmitis without the preceding meningeal infection. METHODS: A 45-year-old female with a history of long-term use of systemic corticosteroid and cytotoxic drugs for systemic lupus erythematosus suffered from progressive visual loss in her left eye over 1 month. Large exudative retinal detachment and severe vitreous infiltration were observed. RESULTS: Histopathologic study of the retinal biopsy specimen established the diagnosis of cryptococcal endophthalmitis. Subsequent positive histopathologic study of the aspiration vitreous smear and epiretinal membrane confirmed the recurrence and persistence of the disease over 4 months after the initial presentation. Systemic amphotericin B-fluconazole and two doses of intravitreous amphotericin B injection eliminated the infection successfully. CONCLUSION: The authors report here a well-documented case of cryptococcal endophthalmitis and present the serial clinical and histopathologic pictures. The importance of retinal biopsy in diagnosis and the combined form of antifungal treatment also are shown.     

The use of dihydrocodeine for postoperative analgesia in gynecological operations

16 patients received twice daily 60-90 mg DHC-Continus. The evaluation of the pain was done with use of visual linear scale from 1-10 (Scott-Huskisson). Four complications occurred: headache, nausea, vomiting, constipation. The authors conclude that the orally administration of DHC is an effective alternative for postoperative treatment of pain in gynecological patients.     

Does the preoperative administration of ketorolac improve postoperative analgesia

AIM OF THE STUDY: 1) To verify the usefulness of ketorolac administration (30 mg i.v.) before a surgical operation in terms of postoperative analgesia improvement; 2) To evaluate the impact of preoperative ketorolac administration on perioperative renal function and on intraoperative water balance; 3) to evaluate the presence of adverse effect due to preoperative NSAID use. DESIGN: Prospective randomized trial. SETTING: University surgical department. PATIENTS AND METHODS: Forty adult patients undergoing major abdominal surgery, randomized in 2 groups: in group 1 ketorolac (30 mg i.v.) was administered immediately after the induction and, for postoperative analgesia, ketorolac (30 mg i.v.) was administered beginning at the time of skin closure; in group 2 no ketorolac was administered before the operation and postoperative treatment was the same. Buprenorphine (0.3 mg i.m.) was administered in case of unsatisfactory analgesia. Fluids infused and diuresis were measured intraoperatively. One, 6 and 24 hours after the end of operation pain was evaluated using pain intensity score and VAS. The day after the operation serum creatinine and urea were measured. RESULTS: No statistically significant differences were found between groups regarding fluids infused, intraoperative diuresis, postoperative pain, adverse effects and number of bleeding episodes. More than 50% of patients, in either groups, required opioids administration. CONCLUSIONS: Ketorolac (30 mg i.v.) administration before a major abdominal operation does not improve postoperative analgesia nor determines significant alterations in renal function or increase in the frequency of abnormal bleedings. Opiate administration is necessary in more than 50% of the patients to achieve adequate analgesia.     

Evaluation of preincisional mexiletine administration to alleviate postoperative pain

Mexiletine, an antiarrhythmic agent, was preincisionally administered intravenously for the purpose of reducing postoperative pain. Twenty-eight female patients for mastectomy were studied. The patients were divided into three groups. Group 1 received no mexiletine. Group 2 received bolus administration of mexiletine 1 mg.kg-1 with additional continuous administration of 1 mg.kg-1.hr-1 for 75 minutes. Group 3 received bolus administration of mexiletine 2 mg.kg-1. The requirement of butorphanol as a postoperative analgesic within 1 hour after mastectomy in Group 3 was significantly lower than that in Group 1 (P < 0.05), but butorphanol requirement in Group 2 was not significantly lower than that in Group 1. Plasma mexiletine concentration was slightly higher in Group 3 (1.7 micrograms.ml-1) than that in Group 2 (1.0 microgram.ml-1) immediately after the intravenous mexiletine administration, although there was no significant difference. The results indicate that mexiletine 2 mg.kg-1 as preoperative bolus administration maintains its plasma concentration above 1.7 micrograms.ml-1, and is clinically effective for reducing the postoperative pain after mastectomy.     

Newborn tissue concentrations of bupivacaine following maternal epidural administration during labor in guinea pigs

Newborn plasma concentrations of maternally administered bupivacaine are often measured, but it is unclear how well they reflect tissue concentrations. Bupivacaine (0.25%) was administered epidurally (0. 12 ml/kg) 10 min prior to labor induction in 6 term-pregnant guinea pigs. Plasma, brain, heart and liver samples were obtained for bupivacaine analysis from newborns (n = 22) after spontaneous delivery. Liver bupivacaine concentrations were 2-3 times greater than those in the plasma, brain, and heart. A similar pattern of tissue concentrations was seen in a smaller number of newborns delivered by cesarean section. Liver bupivacaine concentration decreased with drug-delivery interval in littermates, while heart and brain concentrations showed no relationship with drug-delivery interval. Blood gases of newborns reflected acidosis, which may have influenced tissue drug concentrations. Under conditions of the study, bupivacaine concentrations in heart and brain, potential sites of bupivacaine action, were lower than those observed in a peripheral blood sample.     

The effect of peritoneal air exposure on postoperative tumor growth

Botulinum toxin A has been used to treat wrist and finger spasticity mainly through injection of the forearm flexor muscles. This case study describes its first reported use in managing spastic lumbricals of the hand. A 19-year-old male had significant flexion deformity and hypertonicity of the left wrist and hand, particularly the second through fifth metacarpophalangeal joints, after traumatic brain injury. By using the 0-4 Ashworth scale, spasticity of the lumbricals across the second to fourth metacarpophalangeal joints was rated 2, with persistent clonus of the finger flexors as confirmed by electromyography to the middle and ring fingers, even after botulinum toxin A injection of the flexor digitorum sublimis and profundus muscles. By using the electromyography-guided technique, botulinum toxin A was injected into the first lumbrical of the index finger (12 units), second and third lumbricals of the middle and ring fingers, respectively (15 units each), and fourth lumbrical of the little finger (10 units). At follow-up, clinical and electromyographic examination revealed a significant reduction in tone and clonus of the injected lumbricals. Ashworth scores of the lumbricals from the index to little finger improved to 1. Botulinum toxin A injection of the lumbricals can be beneficial in managing spasticity of these muscles. It is well tolerated and effective at doses of 10 to 15 units. Lumbrical injection of botulinum toxin A is a useful adjunct in our percutaneous armamentarium for managing the spastic hand.     

The effect of epidural injection of betamethasone or bupivacaine in a rat model of lumbar radiculopathy

STUDY DESIGN: The effect of epidural injection of betamethasone or bupivacaine was investigated in an animal model of lumbar radiculopathy. OBJECTIVE: To investigate the effects of an epidural steroid (betamethasone) or a local anesthetic (bupivacaine) in an animal model of radiculopathy produced by nerve root irritation. SUMMARY OF BACKGROUND DATA: Epidural injections are commonly used for the treatment of low back pain and sciatica. However, efficacy remains controversial, and there is a paucity of basic information to support clinical use or the injections. METHODS: Fifty-one rats were used. The left L4 and L5 nerve roots were loosely ligated with chromic gut, and either betamethasone, bupivacaine, betamethasone in combination with bupivacaine, or saline was injected using an epidurally placed catheter. The effects of epidural injection were evaluated using response to noxious stimuli and immunohistochemical methods. RESULTS: In betamethasone-treated rats (either alone or in combination with bupivacaine), thermal hyperalgesia was significantly less (P < 0.010 after surgery than that in saline- or bupivacaine-treated groups, in which the hyperalgesia was maximum at 2-3 postoperative weeks before resolving 5 weeks after surgery. Immunohistochemical analysis did not correlate with these results. CONCLUSIONS: Epidural steroid injection has a significant effect on the thermal hyperalgesia produced in a model of radiculopathy, which may provide clinical support for advocates of epidural steroids.