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PubMed2003

Antinociceptive properties of neurosteroids: a comparison of alphadolone and alphaxalone in potentiation of opioid antinociception.

In this study, we investigated the antinociceptive and sedative effects of the opioids fentanyl, morphine, and oxycodone given alone and in combination with two neurosteroids: alphadolone and alphaxalone. An open-field activity monitor and rotarod apparatus were used to define the sedative effects caused by opioid and neurosteroid compounds given alone intraperitoneally to male Wistar rats. Dose-response curves for antinociception were constructed using only nonsedative doses of these drugs. At nonsedating doses, fentanyl, morphine, and oxycodone all caused dose-dependent tail flick latency (TFL) antinociceptive effects. Because neither neurosteroid altered TFL, electrical current was used as the test to determine doses of neurosteroid that caused antinociceptive effects at nonsedative doses. Alphadolone 10 mg/kg intraperitoneally caused significant antinociceptive effects in the electrical test but alphaxalone did not. All three opioid dose-response curves for TFL antinociception were shifted to the left by coadministration of alphadolone even though alphadolone alone had no effect on TFL. Alphaxalone given alone had no antinociceptive effects at nonsedative doses and it had no effect on opioid antinociception. Neither neurosteroid caused sedative effects when combined with opioids. We conclude that coadministration of alphadolone, but not alphaxalone, with morphine, fentanyl, or oxycodone potentiates antinociception and that this effect is not caused by an increase in sedation.

Analgesics, Opioid↗

PubMed1984

Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.

The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability.

Acetanilides↗

PubMed1981

Adverse effects of commonly ordered oral narcotics.

Approximately equianalgesic oral doses of codeine, an oxycodone compound resembling Percodan, and pentazocine were compared for adverse effects in a double-blind, randomized study of four doses of each drug given over two days to 247 postsurgical patients with pain. Placebo and parenteral morphine were also treated as negative and positive controls, respectively. Approximately 50 patients each received one of the five drugs. Codeine, pentazocine, and morphine had the same incidence of adverse effects (22 to 28 per cent). One capsule of oxycodone compound was the analgesic equivalent of 12.5 mg morphine with an adverse effect incidence of 4 per cent (placebo 8 per cent). Smoking made no difference in analgesic effect or adverse effects. Analgesics given in the evening intervening between the two days may have affected the analgesic performance of placebo.

Administration, Oral↗

PubMed1991

Histamine release induced by opioid analgesics: a comparative study using porcine mast cells.

Studies in vitro have demonstrated histamine release induced by opioid analgesics from rat peritoneal mast cells and human skin mast cells. In humans, elevated plasma histamine levels have also been found following intravenous or oral administration. This study compared the reactivity of five opioid analgesics on mast cell suspensions obtained from porcine heart, kidneys, liver and lungs. The five compounds investigated were hydromorphone, levomethadone, morphine, pethidine and oxycodone. Both morphine and hydromorphone produced little histamine release from all cell types tested. The other drugs demonstrated clear differences between the different cell populations. Thus, the cardiac cells responded most strongly to oxycodone but were the least responsive to pethidine. These differences, if confirmed in vivo, could indicate which drugs may be more suitable for patients with different underlying disease states.

Analgesics, Opioid↗

PubMed2005

No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients.

GOALS OF WORK: The aims of this study were (1) to prospectively evaluate the clinical benefits of switching from morphine to an alternative opioid, using oxycodone as first-line alternative opioid, in patients with cancer, (2) to evaluate the consistency of the clinical decision for the need to switch by comparing two hospital sites, and (3) to evaluate whether there were objective predictors that would help identify morphine non-responders who require switching to an alternative opioid and from this to construct a clinical model to predict the need to switch. PATIENTS AND METHODS: One hundred eighty-six palliative care patients were prospectively recruited from two hospital sites. Responders were patients treated with morphine for more than 4 weeks with good analgesia and minimal side effects. Non-responders (switchers) were patients who had either uncontrolled pain or unacceptable side effects on morphine and therefore required an alternative opioid. The differentiation between responders and switchers was made clinically and later confirmed by objective parameters. RESULTS: In this prospective study 74% (138/186) had a good response to morphine (responders). One patient was lost to follow up. Twenty-five percent (47/186) did not respond to morphine. These non-responders were switched to alternative opioids (switchers). Furthermore, of 186 patients, 37 achieved a successful outcome when switched to oxycodone and an additional 4 were well controlled when switched to more than one alternative opioid. Overall successful pain control with minimal side effects was achieved in 96% (179/186) of patients. There were no significant differences in the need to switch between the two hospital sites. CONCLUSIONS: This study has shown that proactive clinical identification and management of patients that require opioid switching is reproducible in different clinical settings and significantly improves pain control. Further studies are required to develop and test the predictive model.

Adult↗

PubMed2006

Opioid analgesics and rates of fatal drug poisoning in the United States.

OBJECTIVE: To determine whether the variability in rate of sale of prescription opioid analgesics is related to the variability in rates of drug poisoning mortality among states in the United States in 2002. METHODS: Drug poisoning deaths were defined as unintentional deaths or those of undetermined intent whose underlying cause was coded to "narcotics" (X42) or "other and unspecified" drugs (X44) in the National Vital Statistics System. Per capita sales of ten opioid analgesics from the Drug Enforcement Administration and combined sales in morphine equivalents were correlated with drug poisoning mortality rates by state using multivariate linear regression. Regression coefficients between mortality rates and sales rates were adjusted for race (percent white, percent black) and age (percent aged 24 years or younger, and percent aged 65 years and older). RESULTS: There was over a ten-fold variability in sales of some opioid analgesics. Combined sales ranged 3.7-fold, from 218 mg per person in South Dakota to 798 mg per person in Maine. Drug poisoning mortality varied 7.9-fold, from 1.6/100,000 in Iowa to 12.4/100,000 in New Mexico. Drug poisoning mortality correlated most strongly with non-OxyContin oxycodone (r=0.73, p<0.0001), total oxycodone (r=0.68, p<0.0001), and total methadone (r=0.66, p<0.0001) in the multivariate analysis. A scatterplot demonstrated a linear relationship between total opioid analgesic sales and drug poisoning mortality. CONCLUSIONS: The extent of opioid analgesics use varies widely in the United States. Variation in the availability of opioid analgesics is related to the spatial distribution of drug poisoning mortality by state.

Analgesics, Opioid↗

PubMed1998

Affinity profiles of novel delta-receptor selective benzofuran derivatives of non-peptide opioids.

Highly selective heterocyclic opioid ligands with potent delta-antagonist activity have been developed on the basis of the "message-address" concept. Using this strategy, benzofuran derivatives corresponding to the non-selective opioid antagonist, naloxone, and to the mu-opioid receptor selective agonists, oxymorphone and oxycodone, were synthesized. In vitro opioid receptor binding profiles and agonist/antagonist character of these compounds were determined in rat brain membrane preparations with highly selective radioligands. All three benzofuran derivatives displayed high affinities for the delta-opioid receptor, much less potency toward the mu-binding site, and were the least effective at the kappa-site. The results indicated that the addition of the bezofuran moiety to these fused ring opioids confers delta-receptor selectivity. The Na+ indices suggested a partial agonist character for oxymorphone- and oxycodone-benzofuran, and an antagonist character for naloxone-benzofuran. These compounds were capable of irreversible inhibition of opioid binding sites in a dose-dependent.

Animals↗

PubMed2002

Interscalene brachial plexus block is superior to subacromial bursa block after arthroscopic shoulder surgery.

BACKGROUND: Arthroscopic shoulder surgery is often associated with severe postoperative pain. The results concerning subacromial bursa blockade (SUB) as a method of pain relief have been contradictory. We hypothesized that a SUB and interscalene brachial plexus block (ISB) would similarly reduce early postoperative pain and the need for oxycodone as compared to placebo (PLA). METHODS: Forty-five patients scheduled for arthroscopic shoulder surgery were enrolled in this randomised, prospective study. The ISB and SUB blockades were performed with 15 ml of ropivacaine (5 mg/ml). In the PLA group, 15 ml of 0.9% saline was injected into the subacromial bursa. All patients received general anaesthesia. RESULTS: The mean intravenously patient-controlled delivered oxycodone consumption during the first 6 h was significantly lower in the ISB group (6 mg) than in the SUB group (24.1 mg; P=0.001) or in the PLA group (27 mg; P<0.001). No significant differences were detected between the SUB and PLA groups (P=0.791). The postoperative pain scores during the first 4 h at rest and during the first 6 h on movement were significantly lower in the ISB group than in the SUB and PLA groups. CONCLUSION: After arthroscopic shoulder surgery SUB has a minor effect only on postoperative analgesia, whereas an ISB with low-dose ropivacaine effectively relieves early postoperative pain and reduces the need for opioids.

Amides↗

PubMed2003

The terminal cancer patient: effects of age, gender, and primary tumor site on opioid dose.

OBJECTIVE: The objective of the current study is to describe correlations between age, gender, and primary cancer site and sustained-release opioid doses prescribed for hospice patients at the end of life. PATIENTS AND SETTING: This study included all 7,201 hospice patients referred to a North American palliative care specialty pharmacy with the primary diagnosis of cancer and who were prescribed transdermal fentanyl, sustained-release oral morphine, or sustained-release oxycodone. DESIGN: This is a retrospective analysis of the final sustained-release morphine, oxycodone, or transdermal fentanyl doses prescribed to cancer patients, according to pharmacy records. Comparisons between sex and age group were performed with chi-square tests. Mann-Whitney U tests were used to compare mean doses between the sexes. Analyses of covariance (ANCOVA) were used to compare opioid doses between genders and among primary cancer sites while controlling for age. RESULTS: The inverse association between age group and dose was highly significant. For example, final opioid doses </=120 mg/day oral morphine equivalent were prescribed for only 46.4% of patients between 40 and 49 years of age compared with 86.4% of patients 90 years of age and older. An ANCOVA on the largest non-sex-related diagnoses found primary tumor site and patient age, but not gender, to be associated with sustained-release opioid dose. CONCLUSIONS: Both primary tumor site and patient age were associated with final opioid dose. Further investigation is warranted to determine which primary tumor sites are associated with unusually high opioid doses and may highlight the need to optimize adjuvant medication therapy if neuropathic and/or inflammatory pain mechanisms are involved and to refer to pain specialists when appropriate.

Age Factors↗

PubMed2003

Medico-legal rounds: medico-legal issues and alleged breaches of "standards of medical care" in opioid rotation to methadone: a case report.

OBJECTIVES: The objectives of this medico-legal case report were the following: 1) To present an example of a medico-legal problem that developed as a result of a decision to rotate a chronic pain patient (CPP) to methadone in order to taper the CPP from oxycodone; 2) To present both the plaintiff's and defendant's expert witnesses' opinions as to if and where the care of that patient fell below the "standard of medical care;" and 3) Based on these opinions, to develop some recommendations on how, in the future, pain medicine physicians and other physicians should proceed, in order to avoid allegations of breach of "standards of care" when using methadone. METHODS: This is a case report of a CPP treated at a regional hospital pain clinic. Methadone rotation was used in order to taper the CPP from oxycodone because of addictive disease. RESULTS: During the rotation process, the CPP expired. This had medico-legal consequences. Expert witnesses differed as to whether methadone caused the death. CONCLUSION: Pain physicians should proceed with caution in using methadone for opioid rotation.

Adult↗

PubMedDate not supplied

Paravertebral somatic nerve block compared with peripheral nerve blocks for outpatient inguinal herniorrhaphy.

BACKGROUND: Inguinal herniorrhaphy (IH) is a common outpatient procedure, yet postoperative pain and anesthetic side effects remain a problem. Paravertebral somatic nerve blocks (PVB) have the potential to offer unilateral abdominal wall anesthesia and long-lasting pain relief with minimal side effects. We compared PVB with peripheral neural blocks for outpatient IH. METHODS: Forty-six patients scheduled for IH were entered into this prospective, single-blind study. All patients underwent a standardized general anesthetic. Patients were randomly assigned to receive a PVB (levels T10-L2) preoperatively (n = 24) or an intraoperative peripheral block (PB) by the surgeon (n = 22), using 0.5% ropivacaine (40 mL). Opioid use, verbal analog pain scores, and side effects were documented for 72 hours. RESULTS: The use of opioids during surgery was less for the PVB group 162 +/- 70 mg than the PB group, 210 +/- 60 (P =.02). Need for opioids in PACU was less for the PVB group (39%) than the PB group (61%) (P =.002). Time until first pain after discharge was not different between groups, 312 +/- 446 minutes (PB) and 425 +/- 384 minutes (PVB) (P =.12). Of the PVB patients, 29% used no opioids at all compared with 18% of PB patients (P =.12). Mean time until first oxycodone use was similar between groups, 303 +/- 469 minutes (PB) and 295 +/- 225 minutes (PVB) (P =.18). Oxycodone use was also similar; 35 +/- 34 mg (PVB) versus 49 +/- 42 mg (PB) (P =.30). More patients in the PB group (50%) required antiemetic treatment in the postanesthesia care unit than the PVB group (21%) (P <.001). Side effects were similar at all other measurements. CONCLUSIONS: This study shows that PVB provides analgesia equivalent to extensive peripheral nerve block for inguinal herniorrhaphy, offering an alternative method of postoperative pain management and perhaps fewer side effects.

Abdominal Wall↗

PubMed2001

Interscalene brachial plexus block with continuous intraarticular infusion of ropivacaine.

Providing intraarticular analgesia with a continuous infusion of local anesthetic via a disposable infusion pump has gained popularity. Despite the prevalence of this technique, data comparing this method of analgesia to conventional regional anesthesia are not available. We present a prospective study that compared a single-dose interscalene block with a single-dose interscalene block plus continuous intraarticular infusion of local anesthetic. Forty patients scheduled for shoulder arthroscopy were entered in this prospective, double-blinded study. All patients received an interscalene brachial plexus block as their primary anesthetic. Patients were randomly assigned to 1 of 2 groups: 1. interscalene block with 1.5% mepivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.5% ropivacaine at 2 mL/h, or 2. interscalene block with 0.5% ropivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.9% saline (placebo) at 2 mL/h. Postoperative infusions were maintained for 48 h. Visual analog scale pain scores and postoperative oxycodone consumption were measured for 48 h. Visual analog scale scores at rest and with ambulation in the Mepivacaine/Intraarticular Ropivacaine group were reduced when compared with the Ropivacaine/Saline group (rest: P = 0.003, ambulation: P = 0.006). Oxycodone consumption was also decreased (28 +/- 21 mg vs 44 +/- 28 mg, P = 0.046), respectively. We conclude that a brachial plexus block with 1.5% mepivacaine and a continuous intraarticular infusion of 0.5% ropivacaine at 2 mL/h provides improved analgesia for minor surgery at 24 and 48 h versus a single-injection interscalene block with 0.5% ropivacaine.

Adult↗

PubMed1998

Opioid therapy for chronic noncancer back pain. A randomized prospective study.

STUDY DESIGN: A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. OBJECTIVES: To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. METHODS: All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. RESULTS: Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. CONCLUSIONS: The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.

Activities of Daily Living↗

PubMed2004

Patterns and trends in opioid use among individuals with back pain in the United States.

STUDY DESIGN: Secondary analysis of Medical Expenditure Panel Survey from 1996 to 1999. OBJECTIVE: To examine patterns in opioid use in 1996, 1997, 1998, and 1999 among individuals with back pain in the United States and to investigate trends in the use of overall and individual opioid category. SUMMARY OF BACKGROUND DATA: To the authors' best knowledge, no study has examined at a national level the patterns and trends in opioid use among individuals with back pain in the United States. METHODS: Individuals with back pain were stratified by sociodemographic characteristics and geographic regions. Rates of overall opioid use were compared among different strata by the use of simple and multivariate logistic regression models. To investigate trends in opioid use, use rates of the overall and individual opioid category in each year were calculated and compared. RESULTS: From 1996 to 1999, wide variations in overall opioid use were consistently observed among individuals with different educational levels, family income, and health insurance status. Regional variation in opioid use was also observed for most of the 4 years. After adjustment for covariates, health insurance status and geographic regions were consistent predictors of opioid use from 1997 to 1999. Trend analysis indicated that the rates of overall opioid use increased slightly across the 4-year span. Among individual opioid categories, the use of oxycodone or hydrocodone increased, whereas the use of propoxyphene decreased. CONCLUSIONS: The variation in overall opioid use among individuals with back pain with different sociodemographic characteristics and from different geographic regions suggested an opportunity to improve opioid prescribing patterns. The increase in the use of hydrocodone and oxycodone indicated a need to better assess the efficacy and safety associated with these drugs among individuals with back pain.

Adolescent↗

PubMed2006

Trends and geographic variation of opiate medication use in state Medicaid fee-for-service programs, 1996 to 2002.

BACKGROUND: Although studies have documented hospital and surgical service geographic variability, prescription use geographic variability is largely unknown. Opiate pain medications are widely used, particularly because the promulgation of clinical guidelines promoting aggressive pain treatment. This study describes temporal and interstate variability in aggregate prescription opiate medication use within U.S. Medicaid programs. METHODS: A dataset of 49 states' fee-for-service (FFS) Medicaid prescription drug dispensing records from 1996 to 2002 was compiled and used to quantify medication dispensing examining all opiates, controlled release oxycodone, and methadone. The defined daily dose (DDD) per 1000 FFS Medicaid adult enrollees per day was calculated for all opiate medication categories. A market basket of nonpain prescription medications was constructed for comparison. Rates, trends, and the coefficient of variation were determined overall, by year and for each state. RESULTS: From 1996 to 2002, overall use of opiate pain medications increased 309%. The market basket use increased 170%. Total opiate dispensing varied widely from state to state, with a range of 6.9 to 44.1 DDD/1000/d in 1996, and 7.1 to 165.0 DDD/1000/d (a 23-fold difference) in 2002. The coefficient of variation was 49.6 in 2002. Controlled release oxycodone and methadone had a greater rate of increase compared with all opiates. CONCLUSIONS: The dispensing of opiate medications in Medicaid programs increased at almost twice the rate of nonpain-related medications during the 7-year study period. Large, unexplained geographic variation in aggregate use exists. The impact of Medicaid cost-containment strategies on utilization and outcomes should be investigated.

Analgesics, Opioid↗

PubMed1986

Comparison of different methods of postoperative analgesia after thoracotomy.

Fifty-one patients scheduled for thoracotomy were included in a study involving five different methods of postoperative analgesia. Forty patients were randomly divided into: Group C, receiving intramuscular oxycodone on request following an intraoperative intercostal block; Group IC, intercostal blocks with 0.5% bupivacaine performed prior to surgery, 6 h later and on the first postoperative morning: Group EB, epidural bupivacaine as a continuous infusion of 0.25% bupivacaine (5 ml h-1); Group EM4 epidural morphine 4 mg injected prior to surgery and on the first postoperative morning. In addition, a fifth group (Group EM6) of 11 patients received 6 mg of epidural morphine timed as in Group EM4, but these patients were automatically scheduled to be observed in the ICU. Additional intramuscular oxycodone was given on request to all patients. Group EB, EM4 and EM6 had lower numbers of requests than Group C. Pain intensity score was lowest (2.5 on a scale from 0 to 10, 3 h postoperatively) in Group EM6, and there was a statistically significant difference in pain intensity at 3 h between EM4 and EM6. The evaluation of cooperation and pain by the physical therapist revealed no differences between the groups. Postoperative blood-gas analyses contained slightly elevated PCO2 values (6.0-7.3 kPa) in all groups. Postoperatively, only Group EB was devoid of PCO2 values above 7.3 kPa. Urinary retention was a common complication in the patients receiving epidural analgesia, occurring most frequently in Group EM6; 10 of the 11 patients had to be catheterized.

Adult↗

PubMed1991

Failure of transcutaneous electrical nerve stimulation and indomethacin to reduce opiate requirement following cholecystectomy.

This randomized study examined the effect of transcutaneous electrical nerve stimulation (TENS) and indomethacin on postoperative opiate requirement in 60 patients after cholecystectomy. An open intravenous bolus of 25 mg of indomethacin followed by an infusion of 5 mg in 1 h, alone or combined with either low or high frequency TENS, was administered during the study period of 16 h. An intravenous bolus of either 5 mg of oxycodone or 0.15 mg of buprenorphine was administered double blindly for postoperative pain relief. The number of doses of buprenorphine given (3, 9) differed (P = 0.01) from the number of doses of oxycodone given (5, 4). Neither indomethacin nor TENS reduced the postoperative opiate requirement.

Buprenorphine↗

PubMed1994

Effects of intrathecal clonidine on duration of bupivacaine spinal anaesthesia, haemodynamics, and postoperative analgesia in patients undergoing knee arthroscopy.

Clonidine, an alpha-2-adrenergic agonist, may have a clinically relevant analgesic action but also a hypotensive action, when administered spinally. In this study, therefore, the analgesic and circulatory effects of intrathecal clonidine were studied in patients undergoing knee arthroscopy under spinal anaesthesia. Forty ASA I-II patients were randomly divided to two groups. One group received clonidine 3 micrograms.kg-1 mixed with 15 mg 0.5% bupivacaine and the other group an identical saline volume mixed with bupivacaine as above, in a double-blind fashion. Sensory analgesia, blood pressure, heart rate and sedation were followed during and after the operation. Oxycodone 0.14 mg.kg-1 i.m. or ketoprofen 100 mg p.o. was administered when needed. The duration of sensory analgesia (until regression of the block to L2) was longer in the clonidine group (mean 217 min) than in the control group (mean 160 min) (P < 0.05). Duration of motor blockade was also longer in the clonidine group (mean 215 min) compared to the control group (161 min) (P < 0.05). Mean arterial pressure and heart rate were significantly lower in the clonidine group compared to the control group. The clonidine patients needed fewer supplemental doses of oxycodone (8 doses) than those in the control group (16 doses) (P < 0.05). More patients in the clonidine group were sedated 3-6 h after the injection (P < 0.05). Addition of clonidine prolonged the bupivacaine spinal block. However, marked haemodynamic changes and sedation may limit the usefulness of intrathecal clonidine.

Adolescent↗