Administration Of Bupivacaine Research Articles

Bupivacaine for pain reduction after iliac crest bone graft harvest.

Iliac crest bone graft remains the gold standard in achieving spinal arthrodesis, but chronic pain from graft harvest occurs in up to 39% of patients. Studies have shown that a single administration of local anesthetic reduces short-term pain, but they have not adequately investigated possible longer-term benefits. The goal of this study was to determine whether local administration of bupivacaine after iliac crest bone graft harvesting reduces pain and improves patient-reported outcomes. In this prospective, randomized, controlled, and blinded clinical study, 40 patients were identified who underwent posterior spine fusion with iliac crest bone graft and were randomized to receive either bupivacaine (treatment group, n=20) or saline (control group, n=20) at the iliac crest bone graft site. Pain at the harvest site was determined by a series of 12 visual and numeric pain scale assessments. Short Form-12 mental and physical component scores, EuroQol-5D, and Oswestry Disability Index assessments were made, along with determination of patient satisfaction and self-reported outcome of surgery. Baseline pain and outcome assessments were statistically similar (P>.05). Average pain scores were lower for all 12 assessments in the treatment group at mean follow-up of 5 weeks (significant differences in 6 assessments) and 20 weeks (significant differences in 2 assessments). No significant differences were found in Short Form-12 and EuroQol-5D scores. For patients who underwent lumbar fusion, the treatment group had significantly improved Oswestry Disability Index scores (mean±SD=10.8±7.1 vs 18.7±5.9, P=.012). Significantly more patients in the treatment group reported that surgery met all expectations (90% vs 50%, P=.016). This study is the 1st to show that a single administration of bupivacaine at the iliac crest bone graft harvest site during posterior spine fusion surgery can result in improved outcomes and reduced pain far beyond the anesthetic duration of activity.

A comparative study of efficacy of epidural versus interpleural bupivacaine for post operative analgesia after open cholecystectomy

Background The conventional methods of administering the prescribed doses of intramuscular or intravenous analgesics at fixed time intervals results in widely fluctuating and inadequate plasma level leads to poor post operative pain relief. Despite all advances made in the field of medicine, this symptom called “Pain” has not been combated well. Objective The present study was carried out to compare the efficacy of epidural verses interpleural administration of bupivacaine(0.5%) with adrenaline for post operative pain relieve in patients undergoing open cholecystectomy. Methods We prospectively randomized and compared the post operative pain relieve with the reference of visual analog score (VAS) in patients undergoing elective open cholecystectomy in college of medical sciences-teaching hospital, Bharatpur, Chitwan. Forty adult patients undergoing elective cholecystectomy were divided into two groups. Twenty patients in each group were subjected to a different technique of post-operative analgesia, namely thoracic epidural and interpleural instillation of 0.5% bupivacaine. These two groups were then compared in relation to changes produced in the pain scores, vital parameters and complication and side effects associated with the two techniques. The study was conducted for 24 hour postoperatively. Observation: Both thoracic epidural and interpleural instillation of 0.5% bupivacaine compared favorably with regard to analgesia in the present study. In general, the pain relief following thoracic epidural was more complete compared to interpleural but this was not clinically significant. Conclusion The present study shows that both the techniques are equally effective in providing analgesia following cholecystectomy. However, neither technique rendered the patients completely pain free at all times during first 24 hours. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-4, 15-23 DOI: http://dx.doi.org/10.3126/jcmsn.v9i4.10232

The Effect of Age on the Median Effective Dose (ED50) of Intrathecally Administered Plain Bupivacaine for Motor Block

In this study, we sought to determine the median effective dose (ED50) for motor block of intrathecally administered plain bupivacaine in adults (20-80 years) and to assess the effect of age on ED50 required for motor block. This study was performed in 129 adult patients undergoing transurethral, urological, or lower limb surgery under combined spinal and epidural anesthesia. Patients were stratified according to age as follows: 20 to 30, 31 to 40, 41 to 50, 51 to 60, 61 to 70, and 71 to 80 years. The spinal component of the anesthetic was established by bolus administration of up-and-down doses of 0.75% plain bupivacaine, determined by Dixon's method. The degree of motor block after intrathecal administration of each dose was evaluated by the modified Bromage and hip motor function score. The ED50 values were estimated from the up-and-down sequences using the method of Dixon and Massey and logistic regression. Other end points were included on the basis of sensory block level, duration of motor blockade, hypotension, and vasopressor requirements. ED50 for motor block using intrathecal bupivacaine was 10.22 mg (95% confidence interval [CI], 9.96-10.49 mg) in 20- to 30-, 9.52 mg (95% CI, 9.02-10.07 mg) in 31- to 40-, 8.37 mg (95% CI, 7.56-9.26 mg) in 41- to 50-, 7.30 mg (95% CI, 6.84-7.79 mg) in 51 to 60, 6.55 mg (95% CI, 6.01-7.13 mg) in 61- to 70-, and 5.78 mg (95% CI, 5.01-6.67 mg) in 71- to 80-year-old patients. The maximum cephalic analgesic level was L1-L2 level at 5 minutes and T10-L1 at 10 minutes after administration of intrathecal plain bupivacaine in the 6 age groups. There was a significant difference in the duration of motor blockade among groups. The ED50 for motor block of intrathecally administered plain bupivacaine decreased steeply with advancing age.

Status epilepticus induced by intrathecal bupivacaine use: A case report

Local anesthetics are commonly used as analgesics and anesthetics. Local anesthetics from the amide group may lead to symptoms of the central nervous system (CNS) such as depression, seizures or altered mental state, while they may lead to arrhythmia in the cardiovascular system (CVS). The causes of the neurologic complications observed with spinal local anesthetics are the administration of high doses, rapid entry into the systemic circulation, erroneous administration through the IV route, or the diffusion of the drug towards the cephalic region. Bupivacaine is among the most commonly used local anesthetics from the amide group. However rare, neurological injury after administered bupivacaine can be distressing to patients and their families. In our patient, we have administered bupivacaine through the intrathecal route. Thus, we would like to present a case where status epilepticus in the form of generalised tonic-clonic seizures (GTC) has developed subsequent to the intrathecal administration of bupivacaine.

Age and bupivacaine plasma concentrations following radical cystectomy

Continuous epidural analgesia with bupivacaine for postoperative analgesia can increase its plasma concentrations. Whether this effect can be aggravated with increasing age is unknown. Therefore, bupivacaine concentrations were prospectively monitored in patients undergoing radical cystectomies. We analyzed plasma concentrations of bupivacaine in 38 consecutive patients scheduled for radical cystectomy. All patients received general and epidural anesthesia (10 ml bupivacaine 0.5% followed by bupivacaine 0.375% every 90 min) and postoperative continuous epidural analgesia (bupivacaine 0.25% with sufentanil 0.5 μg/ml). For 4 subsequent days, bupivacaine plasma concentrations were measured and the correlation of bupivacaine plasma concentrations with the patient's age were analyzed. Data (mean ± SD) were analyzed by 2-way ANOVA with post hoc analysis or regression analysis. The median age of the patients was 70 years (range 41-86). Postoperatively, bupivacaine plasma concentrations increased significantly. No correlation of plasma concentrations and age could be found. Maximal bupivacaine concentrations of the younger patients were not different from the older patients. No neurological or cardiovascular symptoms of bupivacaine intoxication were found. In conclusion, continuous epidural administration of bupivacaine leads to increasing plasma concentrations. No age dependent differences in bupivacaine plasma concentrations could be found. Therefore, in our patients with intact liver function, we did not find a reason for an age-related restriction in the use of continuous epidural analgesia.

Epidural administration of ketamine or fentanyl with bupivacaine for postoperative analgesia – A comparative study

The purpose of the study was to compare the analgesic effectiveness of epidural administration of ketamine mixed bupivacaine with fentanyl mixed bupivacaine in the management of postoperative pain. This prospective study was carried out in CMH, Bogra in one calendar year from July 2004 to June 2005. For postoperative pain management 100 patients of both sex, age ranging between 20 to 50 years, ASA physical status I and II scheduled for lower abdominal, pelvic and inguinal surgery were included in the study. All patients were divided into two groups. Epidural catheter was inserted in each patient through space between L3 to L2. Surgery was done under epidural anaesthesia in both groups. In group A (n=50) surgery was done with 0.5% bupivacaine and fentanyl (bupivacaine 1.5 ml/segment + fentanyl 2?g/ml). In group B (n=50) surgery was done with 0.5% bupivacaine and ketamine (bupivacaine 1.5ml/segment + ketamine 0.3mg/kg body weight). Epidural analgesia was continued in postoperative ward with 6 ml 0.25% bupivacaine + fentanyl 2?g/ml in group A and with 6 ml 0.25% bupivacaine + ketamine 0.3mg/kg bodyweight in group B, 4 hourly for 24 hours. The efficacy of analgesia was assessed by using Visual Analogue Scale (VAS) and Verbal Rating Scale (VRS). Mean VAS and mean VRS were less than 3 in both groups, which proved adequate postoperative analgesia. Differences of mean VAS and mean VRS between two groups were statistically not significant. Haemodynamic parameters, respiration and oxygenation were within normal range in both groups. Postoperative complications, like inadequate analgesia, post operative nausea and vomiting (PONV), headache and vertigo were less in both groups. It was observed that epidural administration of both bupivacaine mixed with ketamine and bupivacaine mixed with fentanyl found safe, effective and tolerable for postoperative pain management. DOI: http://dx.doi.org/10.3329/jbsa.v22i1.18097 Journal of BSA, 2009; 22(1): 21-25

Effect of Fentanyl in Spinal Anesthesia With Bupivacaine in Opium Abusers

Background: Spinal anesthesia is a common procedure in the anesthesia. In some studies it has been shown that chronic use of opioids is associated with shorter duration of spinal anesthesia when local anesthetics are applied. Objectives: This trial was conducted in order to determine effect of fentanyl on the duration of spinal block by bupivacaine in chronic opium abusers who undergo spinal anesthesia and have lower thresholds for pain. Patients and Methods: This study was a randomized clinical trial in which 50 opium abusers (25 patients in each group) undergoing lower extremity orthopedic surgeries with spinal anesthesia were selected. The patients were randomly divided into two groups. The study group received 15 mg hyperbaric bupivacaine 0.5% plus 25 μg fentanyl, while the control group received 15mg hyperbaric bupivacaine 0.5% plus 0.25 mL normal saline. Results: All randomly selected cases were male (44.7 ± 13.6 year). The mean duration of sensory block was much longer in the study group (87.8 ± 7.22 minutes) in comparison with the control group (70.47 ± 5.45 minutes) (P < 0.001). There was no statistically significant difference between the two groups regarding their age and duration of surgery. Conclusions: Bupivacaine administration in spinal anesthesia for spinal block has a shortened duration in comparison to the combination of bupivacaine and fentanyl in chronic opium abusers.

Intercostal Administration of Liposomal Bupivacaine as a Prognostic Nerve Block Prior to Phenol Neurolysis for Intractable Chest Wall Pain

ABSTRACTInadequate pain relief from systemic medications is common in patients with advanced malignancy. Chest wall pain secondary to tumor involvement of chest wall structures can be challenging to manage with systemic medications, and occasionally patients benefit from interventional procedures such as intercostal nerve blocks and neurolysis. In this report, the authors describe the case of a 58-year-old woman with advanced non-small cell lung cancer with tumor invasion into the third thoracic rib. After reaching maximum tolerated doses of transdermal fentanyl, oral hydromorphone, and oral ketamine, the patient elected for intercostal nerve blockade and neurolysis. Prognostic nerve blockade was performed using liposomal bupivacaine administered via intercostal approach. This formulation of bupivacaine provided an excellent prognostic blockade, which lasted for approximately 96 hours. This extended period of time allowed the patient to fully evaluate the prognostic blockade, prior to proceeding with neurolysis with phenol. This case suggests that liposomal bupivacaine may be a valuable adjunctive agent for prognostic blockade prior to neurolysis for cancer pain.

Comparative evaluation of intraperitoneal bupivacaine, magnesium sulfate and their combination for postoperative analgesia in patients undergoing laparoscopic cholecystectomy

Background: Various multimodal techniques have been employed time and again to allay visceral pain after laparoscopic cholecystectomy. Aim: The aim of this study was to assess and compare the postoperative pain relief in patients undergoing laparoscopic cholecystectomy with intraperitoneal administration of bupivacaine, magnesium sulfate and their combination. Materials and Methods: Patients were randomly divided into four groups of 20 each. Patients in group I C received 50 ml of 0.9% saline, group II B received 50 ml of 0.25% bupivacaine, group III M received 50 ml of 30 mg/kg magnesium sulfate, while patients in group IV MB received 0.125% of bupivacaine with 15 mg/kg of magnesium sulfate to a total volume of 50 ml after surgery. Postoperatively pain was assessed using visual analog scale (VAS) and postoperative pain (VAS > 3) was managed with intravenous tramadol 50 mg. Time to the first request of analgesia, the total number of analgesic doses of tramadol, the incidence and severity of postoperative shoulder pain in 24 h and presence of complications if any were noted. Results: Demographic profile of patients of all the four groups was comparable and statistically nonsignificant. Intraperitoneal instillation of 0.25% bupivacaine provided longest duration of analgesia for 541.5 ΁ 131.48 min with a significant reduction in the number of doses of intramuscular tramadol in 24 h. Intraperitoneal instillation of 30 mg/kg magnesium sulfate provided analgesia for 82.25 ΁ 35.37 min with no significant reduction in a number of doses of intramuscular tramadol in 24 h when compared to control. Intraperitoneal instillation of mixture of bupivacaine and magnesium sulfate in reduced doses, that is, 0.125% bupivacaine and 15 mg/kg magnesium sulfate provided analgesia for 305 ΁ 65.64 min with a significant reduction in a number of doses of intramuscular tramadol in 24 h. There was reduced incidence and severity of shoulder pain, which was comparable in all the four groups. No significant side-effects were seen in any of the groups. Conclusion: Intrape-ritonel administration of bupivacaine, magnesium sulfate and their combination in reduced doses provides effective postoperative analgesia in laparoscopic cholecystectomy patients though their combination when the doses of both the drugs were reduced to half was less effective than bupivacaine group alone. Furthermore, bupivacaine and magnesium sulfate serve as useful adjuncts to postoperative analgesics.

Efficacy of premixed versus sequential administration of clonidine as an adjuvant to hyperbaric bupivacaine intrathecally in cesarean section.

Background:Density of the drugs injected intrathecally is an important factor that influences spread in the cerebrospinal fluid. Mixing adjuvants with local anesthetics (LA) alters their density and hence their spread compared to when given sequentially in seperate syringes.Aims:To evaluate the efficacy of intrathecal administration of hyperbaric bupivacaine (HB) and clonidine as a mixture and sequentially in terms of block characteristics, hemodynamics, neonatal outcome, and postoperative pain.Setting and Design:Prospective randomized single blind study at a tertiary center from 2010 to 2012.Materials and Methods:Ninety full-term parturient scheduled for elective cesarean sections were divided into three groups on the basis of technique of intrathecal drug administration. Group M received mixture of 75 μg clonidine and 10 mg HB 0.5%. Group A received 75 μg clonidine after administration of 10 mg HB 0.5% through separate syringe. Group B received 75 μg clonidine before HB 0.5% (10 mg) through separate syringe.Statistical analysis used:Observational descriptive statistics, analysis of variance with Bonferroni multiple comparison post hoc test, and Chi-square test.Results:Time to achieve complete sensory and motor block was less in group A and B in which drugs were given sequentially. Duration of analgesia lasted longer in group B (474.3 ± 20.79 min) and group A (472.50 ± 22.11 min) than in group M (337 ± 18.22 min) with clinically insignificant influence on hemodynamic parameters and sedation.Conclusion:Sequential technique reduces time to achieve complete sensory and motor block, delays block regression, and significantly prolongs the duration of analgesia. However, it did not matter much whether clonidine was administered before or after HB.

A Review of the Compatibility of Liposome Bupivacaine with Other Drug Products and Commonly Used Implant Materials

The compatibility of a medication with other drugs and implanted materials is an important factor impacting drug safety and efficacy. The liposomal formulation of the local anesthetic bupivacaine is designed to provide prolonged postsurgical analgesia. Its compatibility with other drugs and materials depends on the compatibility of the drug itself, along with the integrity of liposome and liposomal components. A series of studies was conducted to evaluate the compatibility of liposome bupivacaine with diluents, implanted materials, and other drugs likely to be encountered in the surgical settings in which it is used. Liposome bupivacaine demonstrated compatibility with diluents (normal saline, lactated Ringer's solution) and with implanted materials (silicone, stainless steel, titanium, polypropylene, expanded polytetrafluoroethylene), with little or no change in percent of free bupivacaine, packed particle volume, or particle size distribution; liposome bupivacaine exhibited little or no change in the properties of the test materials. Liposome bupivacaine had clinically meaningful interactions with other local anesthetics, including lidocaine, ropivacaine, mepivacaine, or bupivacaine HCl (at liposome bupivacaine to bupivacaine HCl ratios < 2:1), which resulted in substantial displacement and release of free bupivacaine from liposomes. Liposome bupivacaine may be locally administered after ≥ 20 minutes following local administration of lidocaine, ropivacaine, or mepivacaine. Co–administration of liposome bupivacaine and bupivacaine HCl into the same site should be at ratios ≥ 2:1. Interactions between liposome bupivacaine and epinephrine, corticosteroids, antibiotics, non–steroidal anti–inflammatory drugs, tranexamic acid, and opioid analgesics were not clinically meaningful; liposome bupivacaine may be safely co–administered with these agents. No adverse synergistic effects on liposome bupivacaine were observed in evaluations involving multiple medications compared with each drug's individual effects.

Bupivacaine enhances the magnitude and longevity of HIV-specific immune response after immunization with a CD4 epitope-based DNA vaccine

The development of an effective HIV vaccine is still a major scientific challenge. HIV vaccine trials conducted until now were not able to induce broad neutralizing antibodies or effective cell mediated immune responses. More recently, CD4+ T cells have been shown to play an important role in viral control and better disease prognosis. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4+ T cell responses in BALB/c and in multiple HLA class II transgenic mice. Despite the advantages of DNA vaccines and a large number of clinical trials, it has been a challenge to transfer the success of inducing potent immunity observed in animal models to humans. Here, we sought to evaluate the potential use of bupivacaine, a local anesthetic, as an adjuvant for HIVBr18. We observed that the concomitant administration of the local anesthetic bupivacaine with the DNA vaccine HIVBr18 increased the magnitude of CD4+ and CD8+ T cell responses and cytokine production without compromising their breadth. Furthermore, we demonstrate that coadministration of bupivacaine also impacted the longevity of specific immune responses. Since bupivacaine is used in clinical settings, we believe that this concept may contribute to overcome the limited immunogenicity of DNA vaccines in humans.

Liposome Bupivacaine for Postsurgical Analgesia in Adult Patients Undergoing Laparoscopic Colectomy: Results from Prospective Phase IV Sequential Cohort Studies Assessing Health Economic Outcomes

BackgroundOpioid-based postsurgical analgesia exposes patients undergoing laparoscopic colectomy to elevated risk for gastrointestinal motility problems and other opioid-related adverse events (ORAEs). The purpose of our research was to investigate postsurgical outcomes, including opioid consumption, hospital length of stay, and ORAE risk associated with a multimodal analgesia regimen, employing a single administration of liposome bupivacaine as well as other analgesics that act by different mechanisms. MethodsWe analyzed combined results from 6 Phase IV, prospective, single-center studies in which patients undergoing laparoscopic colectomy received opioid-based intravenous patient-controlled analgesia (PCA) or multimodal analgesia incorporating intraoperative administration of liposome bupivacaine. As-needed rescue therapy was available to all patients. Primary outcome measures were postsurgical opioid consumption, hospital length of stay, and hospitalization costs. Secondary measures included time to first rescue opioid use, patient satisfaction with analgesia (assessed using a 5-point Likert scale), and ORAEs. ResultsEighty-two patients underwent laparoscopic colectomy and did not meet intraoperative exclusion criteria (PCA n = 56; multimodal analgesia n = 26). Compared with the PCA group, the multimodal analgesia group had significantly lower mean total postsurgical opioid consumption (96 vs 32 mg, respectively; P < 0.0001) and shorter median postsurgical hospital length of stay (3.0 vs 4.0 days; P = 0.0019). Geometric mean costs were $11,234 and $13,018 in the multimodal analgesia and PCA groups, respectively (P = 0.2612). Median time to first rescue opioid use was longer in the multimodal analgesia group versus PCA group (1.1 hours vs 0.6 hours, respectively; P=0.0003). ORAEs were experienced by 41% of patients receiving intravenous opioid PCA and 8% of patients receiving multimodal analgesia (P = 0.0019). Study limitations included use of an open-label, nonrandomized design; small population size; and the inability to isolate treatment-related effects specifically attributable to liposome bupivacaine. ConclusionsCompared with intravenous opioid PCA, a liposome bupivacaine-based multimodal analgesia regimen reduced postsurgical opioid use, hospital length of stay, and ORAEs, and may lead to improved postsurgical outcomes following laparoscopic colectomy.

CLINICAL TECHNIQUE: Intrathecal Drug Administration in Turtles and Tortoises

Intrathecal (subdural) administration of anesthetic and analgesic drugs in turtles and tortoises is a novel technique for the induction of spinal anesthesia and analgesia. Possible indications for spinal anesthesia include surgical procedures of the tail, phallus, cloaca, and hind limbs. Intrathecal injections are performed at the level of the coccygeal vertebrae. In red-eared sliders the intrathecal administration of lidocaine (2% preservative free, 4mg/kg) and bupivacaine (0.5% preservative free, 1mg/kg) provides regional anesthesia of the tail, cloaca, and hind limbs for about 1 and 2 hours, respectively. The intrathecal administration of morphine provides regional analgesia for up to 48 hours. Strict aseptic techniques should be used to avoid iatrogenic complications, and only preservative-free drugs should be injected into the intrathecal space so that spinal toxicity and secondary neurologic complications are avoided.

Intraperitoneal bupivacaine for pain relief after minilaparoscopy in patients with infertility

To evaluate the efficacy of intraperitoneal bupivacaine to reduce post operative pain after diagnostic minilaparoscopy in patients with infertility. A prospective randomized study was performed. The study group consisted of 104 women with infertility undergoing diagnostic minilaparoscopy. At the end of the procedure, the treatment group (Group A) was given 10 mL of intraperitoneal 0.25 % bupivacaine (100 mg) and the control group (Group B) given 10 mL of intraperitoneal saline. Post operative pain was recorded with the use of a visual analog scale with scores ranging from 1 to 10 at 2, 4, 6 and 8 h intervals after the surgery. Additional analgesics given to the patients in the post operative period and any other side effects were noted. The treatment group had significantly lower pain scores at 2, 4, 6 and 8 h after the procedure (P < 0.05). The need for post operative analgesics also was significantly lower in the treatment group (P = 0.007). Post operative intraperitoneal bupivacaine administration is beneficial for patients undergoing diagnostic minilaparoscopy. It can significantly decrease post operative pain for up to 8 h and reduce the need for additional analgesics.

Injection of intrathecal normal saline in decreasing postdural puncture headache

Postdural puncture headache (PDPH) is the most common and still unresolved postoperative complication of spinal anesthesia. Although there are several positive results of intrathecal saline injection for the treatment of PDPH and prophylaxis after accidental dural puncture, the effect of deliberate intrathecal saline injection before spinal anesthesia has not been examined. The objective of our study was to evaluate the effect of prophylactic administration of intrathecal normal saline in decreasing PDPH. One hundred healthy women (ASA physical status I) of age between 18 and 35 years scheduled for elective term cesarean delivery under spinal anesthesia were included. Patients were randomly divided into two equal groups. Group C received 2.5 ml (12.5 mg) hyperbaric bupivacaine 0.5 % as a control, and group S received intrathecal normal saline 5 ml before intrathecal injection of 2.5 ml (12.5 mg) hyperbaric bupivacaine 0.5%. The incidence and severity of PDPH were assessed after 48 h and again 3-7 days after operation. Basal characteristics were statistically similar in both groups (P > 0.05). The incidences of moderate and severe PDPH during first postoperative 48 h were not different between the groups (P = 0.24). However, the frequency of PDPH after 3-7 days was statistically higher in group C in compared with group S (16 vs. 2 %, P = 0.03). Totally the frequency of PDPH was higher in group C (24 vs. 2%, P = 0.002). Administration of normal saline (5 ml) before intrathecal administration of hyperbaric bupivacaine as a preventive approach is an effective and simple way to minimize PDPH in patients undergoing cesarean section.

Analgesic and sympatholytic effects of low-dose intrathecal clonidine compared with bupivacaine: a dose–response study in female volunteers

BackgroundA wide range of doses has been suggested for intrathecal clonidine, but no dose-ranging study has examined analgesic effects below 100 µg. The primary aim of this volunteer study was to assess the dose vs analgesic effect relationship for doses of intrathecal clonidine below 100 µg. MethodsAfter IRB approval and signed informed consent, 11 healthy female volunteers participated in this randomized, double-blinded, cross-over study using a dose-ranging sparse-sampling technique. Participants received intrathecal clonidine (doses 0–100 µg; n=10) and intrathecal bupivacaine (doses 0–8.8 mg; n=9) on separate study days. At baseline, 30, and 60 min from drug administration, experimental heat pain tolerance was assessed at both a lumbar and a cranial dermatome. Heat and cold perception thresholds were assessed at the same time intervals. Heart rate (HR), arterial pressure, and forearm–finger and toe-leg cutaneous temperature gradients (Tfinger–arm and Ttoe–leg) were used as measures of sympatholysis. ResultsBoth intrathecal clonidine and bupivacaine caused significant, dose-dependent analgesic effects at the leg but not the head. Significant analgesia to experimental heat pain was detected above 25 µg clonidine and 3 mg bupivacaine. Administration of bupivacaine but not clonidine resulted in a significant dose-related decrease in HR and Ttoe–leg; neither drug caused dose-related sympatholytic effects in the doses used. ConclusionsAfter 50 µg clonidine or 5 mg bupivacaine, the heat pain tolerance increased by ∼1°C, similar to the analgesic effect of 5 mg epidural morphine or 30 µg epidural fentanyl in previous studies using this experimental heat pain model. Our results provide additional data for rational dose selection of intrathecal clonidine.

Efficiency of Bupivacaine Versus Lidocaine and Methylprednisolone Versus Placebo to Reduce Postoperative Pain and Swelling After Surgical Removal of Mandibular Third Molars: A Randomized, Double-Blinded, Crossover Clinical Trial

To compare 4 treatment combinations to reduce postoperative pain and swelling after surgical removal of mandibular third molars. Patients scheduled for bilateral mandibular third molar removal were randomized to 1 of 4 treatment groups in a double-blinded crossover design: 1) first operation: lidocaine and placebo, second operation: bupivacaine and methylprednisolone; 2) first operation: bupivacaine and methylprednisolone, second operation: lidocaine and placebo; 3) first operation: lidocaine and methylprednisolone, second operation: bupivacaine and placebo; 4) first operation: bupivacaine and placebo, second operation: lidocaine and methylprednisolone. Patient-reported pain and swelling were recorded using visual analog scales 2, 4, 6, 8, and 12 hours after surgery and daily during the first postoperative week. The treatment effects were estimated as contrasts between the average differences within the treatment groups and assessed by stratified t tests. A total of 126 patients (57 women and 69 men; mean age, 25.0 years) were included in the analysis. No significant interactions between local analgesia and methylprednisolone were observed. The administration of bupivacaine resulted in less postoperative pain up to 12 hours after surgery (P<.004) and more postoperative swelling 4 to 12 hours after surgery (P < .001) compared with lidocaine. The administration of methylprednisolone resulted in less postoperative pain 4 to 12 hours and 2 days after surgery (P < .05) and less postoperative swelling 6 and 12 hours and 1 to 3 days after surgery (P < .04) compared with placebo. Bupivacaine combined with methylprednisolone reduced the postoperative pain and swelling compared with the use of lidocaine and placebo, lidocaine and methylprednisolone, or bupivacaine and placebo.

An extended paIn relief trial utilizing the infiltration of a long-acting Multivesicular liPosome foRmulation Of bupiVacaine, EXPAREL (IMPROVE): a Phase IV health economic trial in adult patients undergoing ileostomy reversal

BackgroundOpioid analgesics are effective for postsurgical pain but are associated with opioid-related adverse events, creating a significant clinical and economic burden. Gastrointestinal surgery patients are at high risk for opioid-related adverse events. We conducted a study to assess the impact of an opioid-sparing multimodal analgesia regimen with liposome bupivacaine, compared with the standard of care (intravenous [IV] opioid-based, patient-controlled analgesia [PCA]) on postsurgical opioid use and health economic outcomes in patients undergoing ileostomy reversal.MethodsIn this open-label, multicenter study, sequential cohorts of patients undergoing ileostomy reversal received IV opioid PCA (first cohort); or multimodal analgesia including a single intraoperative administration of liposome bupivacaine (second cohort). Rescue analgesia was available to all patients. Primary outcome measures were postsurgical opioid use, hospital length of stay, and hospitalization costs. Incidence of opioid-related adverse events was also assessed.ResultsTwenty-seven patients were enrolled, underwent the planned surgery, and did not meet any intraoperative exclusion criteria; 16 received liposome bupivacaine-based multimodal analgesia and eleven received the standard IV opioid PCA regimen. The multimodal regimen was associated with significant reductions in opioid use compared with the IV opioid PCA regimen (mean, 20 mg versus 112 mg; median, 6 mg versus 48 mg, respectively; P < 0.01), postsurgical length of stay (median, 3.0 days versus 5.1 days, respectively; P < 0.001), and hospitalization costs (geometric mean, $6482 versus $9282, respectively; P = 0.01).ConclusionA liposome bupivacaine-based multimodal analgesic regimen resulted in statistically significant and clinically meaningful reductions in opioid consumption, shorter length of stay, and lower inpatient costs than an IV opioid-based analgesic regimen.

Liposome bupivacaine (EXPAREL&amp;reg;) for extended pain relief in patients undergoing ileostomy reversal at a single institution with a fast-track discharge protocol: an IMPROVE Phase IV health economics trial

BackgroundPostoperative opioid use following ileostomy reversal procedures contributes to postoperative ileus. We assessed the impact of a liposome bupivacaine-based, opioid-sparing multimodal analgesia regimen versus a standard opioid-based analgesia regimen on postsurgical opioid use. We also assessed health economic outcomes in patients undergoing ileostomy reversal at our institution, which employs an enhanced recovery discharge protocol.MethodsIn this single-center, open-label study, patients undergoing ileostomy reversal received postsurgical pain therapy via multimodal analgesia that included a single intraoperative administration of liposome bupivacaine or opioid-based patient-controlled analgesia (PCA) with intravenous morphine or hydromorphone. Rescue analgesia (intravenous [IV] opioids and/or oral opioid + acetaminophen) was available to all patients. Primary efficacy measures included postsurgical opioid use, hospital length of stay (LOS), and hospitalization costs. Secondary measures included: time to first rescue opioid use; patient satisfaction with analgesia; additional medical intervention; and opioid-related adverse events.ResultsForty-three patients were enrolled and met eligibility criteria (IV opioid PCA group = 20; liposome bupivacaine-based multimodal analgesia group = 23). Postsurgical opioid use was significantly less in the multimodal analgesia group compared with the IV opioid PCA group (mean [standard deviation]: 38 mg [46 mg] versus 68 mg [47 mg]; P = 0.004). Postsurgical LOS between-group differences (median: 3.0 days versus 3.8 days) and geometric mean hospitalization costs (US $6,611 versus US$6,790) favored the multimodal analgesic group but did not achieve statistical significance. Median time to first opioid use was 1.1 hours versus 0.7 hours in the multimodal analgesia and IV opioid PCA groups, respectively; P = 0.035. Two patients in the multimodal analgesia group and one in the IV opioid PCA group experienced opioid-related adverse events.ConclusionA liposome bupivacaine-based multimodal analgesic regimen reduced postoperative opioid consumption in patients undergoing ileostomy reversal under a fast-track discharge protocol. A reduction of 21% in LOS (0.8 days) was noted which, although not statistically significant, may be considered clinically meaningful given the already aggressive fast-track discharge program.