Oral Hydrocodone Research Articles

Selective Inhibition of NaV1.8 with VX-548 for Acute Pain

BackgroundThe NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.MethodsAfter establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate–acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate–acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo.ResultsA total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548.ConclusionsAs compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.)

CYP2D in the brain impacts oral hydrocodone analgesia in vivo

Cytochrome P450 2D (CYP2D) metabolises many centrally-acting substrates including opioids. Hydrocodone, an opioid and CYP2D substrate, is metabolised to hydromorphone, an active metabolite. CYP2D in the brain is active in vivo and can alter drug response however, it is unknown whether metabolism by CYP2D in the brain alters oral hydrocodone induced analgesia. Propranolol, a selective CYP2D mechanism-based inhibitor, or vehicle, was administered into the right cerebral ventricle of male rats, (HAN Wistars, Envigo), 24 h before testing for analgesia from oral hydrocodone (or hydromorphone, a non-CYP2D substrate). Hydrocodone and its CYP2D-mediated metabolites were simultaneously quantified using a novel LC-MS/MS assay. After propranolol vs vehicle pretreatment, there was significantly higher analgesia from oral hydrocodone, and a significantly lower brain CYP2D metabolic ratio (an in vivo phenotype of brain CYP2D activity that was derived from the molar sum of hydromorphone and its metabolites divided by hydrocodone). The brain CYP2D metabolic ratio correlated significantly with analgesia. There was no pretreatment effect on plasma hydrocodone concentrations, elimination rates, or metabolic ratio (an in vivo phenotype for hepatic CYP2D activity). The liver CYP2D metabolic ratio did not correlate with analgesia. Propranolol pretreatment had no impact on analgesia from oral hydromorphone. These data suggest that inhibited CYP2D activity in brain, causing reduced metabolism of brain hydrocodone, resulted in higher analgesia from oral hydrocodone, despite hydrocodone having a lower μ-opioid receptor affinity than hydromorphone. Thus, variation in CYP2D in the brain may be an important source of interindividual differences in response to CYP2D substrates, including oral hydrocodone.

(366) Opioid Prescription Practices in the Setting of Pediatric Fractures

Opioids are frequently prescribed to children with fractures. Although much research has been done surrounding the use of opioids in adult populations, use of opioids among children is much less understood. The purpose of this study was to investigate pediatric opioid prescription trends over the last ten years, and to compare prescription practices between doctors of different specialties. We performed a retrospective analysis of all patients age 0-18 who presented to an urban ED between 2007-2017 for fracture care. Data collected included age, opioids given in the ED, opioid prescriptions from the ED, follow-up appointment specialty, and opioid prescriptions from the first follow-up visit. Opioid prescription quantities were assessed in morphine equivalents (MEs). From pilot data of 1,387 patients with fractures, 488 patients (35.2%) received an opioid medication in the ED. Morphine (202, 14.6%) and oxycodone (191, 13.7%) were the most common opioids give in the ED setting though oral hydrocodone and codeine, and IV fentanyl and hydrocodone were also used. Opioid prescriptions from the ED were given to 491 patients (35.4%), with a mean quantity of 111.7 MEs (SD=74.4). 1,059 patients attended a follow-up appointment. 47 of the 844 (6.7%) patients who followed-up with orthopedics, and 14 of the 103 (13.5%) who followed up with plastics received opioid prescriptions. The mean quantity of opioid prescribed at the first follow-up visit was 256.1 MEs (SD=162.9). Preliminary data suggests that larger quantities of opioids are given at follow-up visits than are given in the ED. For pediatric fractures, plastic surgeons prescribe opioids twice as frequently as orthopedic surgeons. The next step for this research to draw comparisons between patients of different age groups and different fracture types.

Evaluation of the Relative Intranasal Abuse Potential of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users.

ObjectiveTo assess the intranasal abuse potential of hydrocodone extended-release (ER) tablets developed with CIMA Abuse-Deterrence Technology compared with hydrocodone powder and hydrocodone bitartrate ER capsules (Zohydro ER, original formulation [HYD-OF]).DesignSingle-dose, randomized, double-blind, quadruple-dummy, active- and placebo-controlled, crossover study.SettingOne US site.SubjectsHealthy, adult, nondependent, recreational opioid users.MethodsSubjects able to tolerate intranasal hydrocodone and discriminate hydrocodone from placebo were eligible for study enrollment. Eligible participants randomly received intranasal hydrocodone ER, intranasal hydrocodone powder, intranasal HYD-OF, intact oral hydrocodone ER, and placebo. Coprimary pharmacodynamic end points were a maximum effect on “at the moment” Drug Liking visual analog scale and Overall Drug Liking visual analog scale. Pharmacokinetics and safety were assessed.ResultsMean maximum effect for “at the moment” Drug Liking was significantly (P < 0.01) lower for intranasal hydrocodone ER (72.8) compared with hydrocodone powder (80.2) and HYD-OF (83.2). Similar results were observed for Overall Drug Liking maximum effect (68.5 vs 77.1 and 79.8, respectively; P < 0.01). Secondary end points, including balance of effects and positive, sedative, and other effects, were consistent with these results. Intranasal treatments showed significantly greater effects vs placebo, while intact oral hydrocodone ER was similar to placebo. For each treatment, plasma concentration-time profiles paralleled “at the moment” Drug Liking over time. Incidences of adverse events for intranasal treatments were 52% for hydrocodone ER, 53% for hydrocodone powder, and 61% for HYD-OF.ConclusionsThe statistically significant differences between hydrocodone ER vs hydrocodone powder and HYD-OF for the primary drug liking end points indicate a lower intranasal abuse potential with hydrocodone ER in healthy, nondependent, recreational opioid users.

Decreasing postoperative narcotics in reconstructive pelvic surgery: a randomized controlled trial

Postoperative pain control is crucial to any successful recovery plan. Many currently used medication regimens are narcotic-focused. The objective of our study was to evaluate the efficacy of a multimodal pain regimen after pelvic reconstructive surgery. The primary outcome measure was narcotic use. Secondary outcomes included pain, nausea, and constipation. Patients were randomized to either usual care postoperative treatment or multimodal pain regimen. Usual care included no specific preoperative or intraoperative medications, and postoperative narcotics with ibuprofen. Multimodal pain regimen included preoperative and postoperative celecoxib, gabapentin, intraoperative and postoperative intravenous and oral acetaminophen and ibuprofen, and narcotics as needed. All narcotics were converted to milligram equivalents of oral morphine for standardization according to Centers for Disease Control and Prevention guidelines where conversion factors for oral hydrocodone= 1, oral oxycodone= 1.5, and oral hydromorphone= 4. Patients were given the validated Brief Pain Inventory survey preoperatively (baseline), at postoperative day 1, and 1 week postoperatively. At 1 week, bowel function and narcotics usage was assessed. Seventy patients were randomized to the usual care arm and 68 to the multimodal pain regimen arm. Patients in the multimodal pain regimen arm used significantly fewer intravenous narcotics in the operating room (90.7 ± 39.1 mg vs 104.6 ± 33.5 mg; P= .026) and while in the hospital (10.8 ± 15.1 mg vs 31.2 ± 29.6 mg; P < .001) and were more likely to use 0 oral narcotics after discharge to home (34.8% of patients vs 10.6%; P= .001). Of the patients who did use oral narcotics after discharge to home, there was no difference in amount used between groups (121.3 ± 103.7 mg in the multimodal pain regimen arm vs 153.0 ± 113.8 mg in the usual care arm; P=.139). Total narcotic usage (operating room+ hospital+ home) was significantly less in the multimodal pain regimen arm of the study (195.5 ± 147.2 mg vs 304.0 ± 162.1 mg; P < .001). There were no significant differences in pain scores between the 2 arms of the study on either postoperative time point. There were no significant differences in antiemetic use while in hospital, consistency of first bowel movement, length of stay, or number of telephone calls to nurses in first 3 weeks postoperatively. A multimodal pain regimen in pelvic reconstructive surgery was found to decrease postoperative opioid requirements, while providing equivalent pain control.

Hydrocodone Bitartrate ER (Hysingla® ER): A Review in Chronic Pain.

Hydrocodone bitartrate extended-release (Hysingla® ER; referred to hereafter as hydrocodone ER) was the first single-entity hydrocodone formulation recognized by the US FDA as having abuse-deterrent properties. It is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Once-daily oral hydrocodone ER provides consistent plasma hydrocodone concentrations and sustained analgesia over the 24-h dosing interval. Its physicochemical properties render hydrocodone ER harder to manipulate physically, which is expected to deter intranasal, intravenous and oral abuse. For instance, oral hydrocodone ER (intact or chewed) significantly reduced drug liking relative to hydrocodone solution in a clinical study. In two large phase III studies in patients with chronic pain, hydrocodone ER reduced pain intensity, with its effects seen early (during dose titration) and maintained during ≤76weeks' treatment. During maintenance therapy, the majority of patients continued hydrocodone ER at the dosage achieved at the end of dose titration and without requiring increased doses of supplemental pain medication, suggesting adequate pain management. Hydrocodone ER was generally well tolerated, with a safety profile consistent with that seen with other μ-opioid analgesics. However, like other opioids, it is associated with risks of addiction, abuse/misuse and serious adverse events (AEs), including respiratory depression, withdrawal, physical dependence and overdose. Although large postmarketing studies are needed to determine whether the abuse-deterrent properties of hydrocodone ER result in meaningful reductions in abuse, misuse and related adverse clinical outcomes, current evidence indicates that hydrocodone ER is a useful treatment option for patients with chronic pain.

Transient low testosterone levels after oral hydrocodone may contribute to misdiagnosis of hypogonadism.

Multiple morning testosterone levels are needed to establish the presence of male hypogonadism and to justify its replacement therapy. Any influence on these levels by short-term opioid ingestion has not, however, been reported. Serial testosterone levels are reported at 2-hour intervals once weekly for 22 weeks in a man after his ingestion of 0, 5, or 10 mg of hydrocodone. Five milligrams of hydrocodone did not significantly alter postingestion testosterone levels, but 10 mg ingestion lowered them at 2, 4, and 6 hours postingestion.

Transient Low Testosterone Levels After Oral Hydrocodone May Contribute to Misdiagnosis of Hypogonadism

Alterations in luteinizing hormones and testosterone levels following short-acting opioid ingestion are unknown but may assist in the diagnosis of hypogonadism in opioid consumers. Serial luteinizing hormones and testosterone values were measured every 2 hours for 10 hours following ingestion of either 0, 5, or 10 mg of hydrocodone on multiple isolated occasions, and demonstrated testosterone levels 2 and 4 hours after 10 mg ingestion to be 25% lower than those after 0 or 5 mg, with this difference resolving within 8 post-ingestion hours, indicating that knowledge of recent hydrocodone ingestion may be valuable in interpreting the significance of low morning testosterone levels in some patients. J Endocrinol Metab. 2016;6(1):18-20 doi: http://dx.doi.org/10.14740/jem324w

A Guide for Pain Management in Developing Nations: The Diagnosis and Assessment of Pain in Cancer Patients

The fundamental approach to cancer patients with pain is to identify the pain sites, and describe, quantify, and categorize the pain by type at each site. There are many validated tools to serve the clinician in these efforts, particularly for pain assessment. Multimechanistic pain syndromes are common in cancer patients. Cancer patients may experience nociceptive pain. They may also experience neuropathic pain due to chemotherapy-induced or cancer-related nerve damage. Analgesic choices must be guided by the pain mechanisms, nature, and severity of the pain, comorbid conditions, and patient characteristics. Long-acting opioid analgesics or fixed-clock dosing can eliminate end-of-dose analgesic gaps. The potential for opioid abuse is an important public health challenge but one that should not undermine the appropriate treatment of moderate to severe cancer pain. Abuse-deterrent opioid formulations can be useful. Care is needed for special populations of cancer patients dealing with pain, such as geriatric, pediatric, or obese patients. While morphine has long been the gold standard of oral opioid products, recent clinical trials suggest that oral hydrocodone and oral oxycodone may offer advantages over oral morphine. Patient adherence is crucial for adequate analgesia and patient education can promote adherence and manage expectations.

Transient Low Testosterone Levels After Oral Hydrocodone May Contribute to Misdiagnosis of Hypogonadism

Transient Low Testosterone Levels After Oral Hydrocodone May Contribute to Misdiagnosis of Hypogonadism

(425) Evaluation of the relative intranasal abuse potential of a hydrocodone extended-release tablet formulated with abuse-deterrence technology in nondependent, recreational opioid users

Misuse and abuse of opioids pose serious public health and safety risks. A hydrocodone bitartrate extended-release (ER) tablet, formulated with CIMA® Abuse-Deterrence Technology, provides resistance against rapid release of hydrocodone when tablets are manipulated or taken with alcohol, potentially reducing abuse liability when misused or abused. This study examined the relative abuse potential of manipulated intranasal hydrocodone ER in healthy nondependent adults with a history of recreational and intranasal opioid use. Subjects able to tolerate a 45-mg intranasal dose of hydrocodone active pharmaceutical ingredient (API) powder and discriminate effects of hydrocodone from placebo were randomized into a double-blind, 5-period crossover, treatment phase to assess abuse potential. Subjects received each of the following: intranasal manipulated hydrocodone ER 45 mg, intranasal hydrocodone API 45 mg, intact oral hydrocodone ER 45 mg, intranasal manipulated Zohydro 45 mg (commercially available hydrocodone ER capsule), and placebo. Forty-five subjects were enrolled; 34 were evaluable for pharmacodynamic assessments performed through 48 hours after administration of study drug. Maximum effect (Emax) of “at this moment” drug liking based on a bipolar Visual Analog Scale (VAS; primary endpoint) was significantly (P=0.004) lower for hydrocodone ER vs. hydrocodone API and Zohydro (72.8 vs. 80.2 and 83.2, respectively) and significantly (P<0.001) higher vs. oral hydrocodone ER (57.3) and placebo (58.6). Emax of end-of-day/next-day Overall Drug Liking VAS (co-primary endpoint) was also significantly (P=0.004) lower for hydrocodone ER vs. hydrocodone API and Zohydro (68.5 vs. 77.1 and 79.8, respectively) and significantly (P≤0.001) higher vs. oral hydrocodone ER (57.8) and placebo (57.7). No new safety signals were observed. Abuse potential via the intranasal route, one of the two most common routes of abuse, was significantly lower with hydrocodone ER compared with non–abuse-deterrent opioid products, including Zohydro. When administered as intended (intact orally), liking scores for hydrocodone ER were similar to placebo. Misuse and abuse of opioids pose serious public health and safety risks. A hydrocodone bitartrate extended-release (ER) tablet, formulated with CIMA® Abuse-Deterrence Technology, provides resistance against rapid release of hydrocodone when tablets are manipulated or taken with alcohol, potentially reducing abuse liability when misused or abused. This study examined the relative abuse potential of manipulated intranasal hydrocodone ER in healthy nondependent adults with a history of recreational and intranasal opioid use. Subjects able to tolerate a 45-mg intranasal dose of hydrocodone active pharmaceutical ingredient (API) powder and discriminate effects of hydrocodone from placebo were randomized into a double-blind, 5-period crossover, treatment phase to assess abuse potential. Subjects received each of the following: intranasal manipulated hydrocodone ER 45 mg, intranasal hydrocodone API 45 mg, intact oral hydrocodone ER 45 mg, intranasal manipulated Zohydro 45 mg (commercially available hydrocodone ER capsule), and placebo. Forty-five subjects were enrolled; 34 were evaluable for pharmacodynamic assessments performed through 48 hours after administration of study drug. Maximum effect (Emax) of “at this moment” drug liking based on a bipolar Visual Analog Scale (VAS; primary endpoint) was significantly (P=0.004) lower for hydrocodone ER vs. hydrocodone API and Zohydro (72.8 vs. 80.2 and 83.2, respectively) and significantly (P<0.001) higher vs. oral hydrocodone ER (57.3) and placebo (58.6). Emax of end-of-day/next-day Overall Drug Liking VAS (co-primary endpoint) was also significantly (P=0.004) lower for hydrocodone ER vs. hydrocodone API and Zohydro (68.5 vs. 77.1 and 79.8, respectively) and significantly (P≤0.001) higher vs. oral hydrocodone ER (57.8) and placebo (57.7). No new safety signals were observed. Abuse potential via the intranasal route, one of the two most common routes of abuse, was significantly lower with hydrocodone ER compared with non–abuse-deterrent opioid products, including Zohydro. When administered as intended (intact orally), liking scores for hydrocodone ER were similar to placebo.

Oral Hydrocodone Induced Acute Psychosis in an Adult Male: A CaseReport.

Hydrocodone is an opioid derived from codeine, which has been used for many years as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen). Common and severe psychiatric side effects included include mental depression, mood changes, hallucination, delirium, somnolence, agitation, and dysphoria. This is a report of a particular case that resulted in acute psychosis after immediately starting on Hydrocodone because of back pain in a 35 year old male, with no past psychiatrist history. The patient returned to his baseline mental status after the hydrocodone was discontinued. Earlier research was published about these symptoms are the ones where hydrocodone was used in combination with other drugs, but in this unique case the patient was not any other medication except the hydrocodone. This unique case showed an association between the short term use of hydrocodone and development of psychiatric symptoms. Recognition of these uncommon psychiatric side effects of hydrocodone usage will allow for early recognition of their etiology, symptoms and treatment. Psychotic symptoms induce by analgesics are not a common condition but they still remain under diagnosed and untreated.

Pharmacokinetics of hydrocodone and hydromorphone after oral hydrocodone in healthy Greyhound dogs

The purpose of this study was to determine the pharmacokinetics of hydrocodone and its active metabolite hydromorphone in six healthy Greyhound dogs. Hydrocodone bitartrate was administered at a targeted dose of 0.5mg/kg PO. Plasma concentrations of hydrocodone and hydromorphone were determined by liquid chromatography triple quadrupole mass spectrometry. The mean hydrocodone CMAX was 11.73ng/mL at 0.74h with a terminal half-life of 1.60h. The mean hydromorphone CMAX was 5.2ng/mL at 1.37h with a terminal half-life of 3.07h. Mean plasma hydromorphone concentrations exceeded 2ng/mL from 0.5 to 8h after hydrocodone administration. Further studies assessing the antinociceptive effects of oral hydrocodone are needed.

Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers

Background Non-medical use and abuse of prescription opioids is a significant problem in the United States. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. The purpose of this study was to directly compare the psychopharmacological profile of two widely prescribed and abused oral opioid combination products within the same subject. Methods Twenty non-drug-abusing volunteers participated in a crossover, randomized, double-blind study in which they received, all p.o.: placebo; 975 mg acetaminophen (ACET); 10 mg oxycodone (OXY)/487 mg ACET; 20 mg OXY/975 mg ACET; 15 mg hydrocodone (HYD)/487 mg ACET; and 30 mg HYD/975 mg ACET. OXY and HYD doses were chosen to equate the drugs on an objective measure of opiate effects: miosis. Dependent measures were subjective, psychomotor/cognitive, reinforcing, and physiological effects, and relative potency estimates. Results In general, the two opioid combination products at equi-miotic doses produced similar prototypic opiate-like effects and psychomotor impairment, and of similar magnitude. The higher dose of OXY/ACET produced slightly more abuse liability-related subjective effects than the higher dose of HYD/OXY, but also produced slightly more negative effects. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated that OXY/ACET was approximately 1.5 times more potent than HYD/ACET. Conclusions Consistent with a recent study published in this journal using identical doses of HYD and OXY (without ACET) in prescription opioid abusers (Walsh, S.L., Nuzzo, P.A., Lofwall, M.R., Holtman Jr., J.R., 2008. The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription drug abusers. Drug Alcohol Depend. 198, 191–202), we found little difference in the pharmacodynamic effects of HYD/ACET and OXY/ACET in non-drug-abusing volunteers.

Continuous Femoral Nerve Block versus Intra-articular Injection for Pain Control after Anterior Cruciate Ligament Reconstruction

Background Continuous femoral nerve blocks have been recommended for postoperative pain control after anterior cruciate ligament reconstruction. Hypothesis A pain control protocol involving a continuous ropivacaine femoral nerve block will decrease pain and narcotic use in the first 24 hours after surgery compared with a postoperative pain control protocol involving an intra-articular injection of bupivacaine/morphine. Study Design Randomized controlled clinical trial; Level of evidence, 2. Methods Ninety subjects, aged 15 years or older, who were receiving arthroscopically assisted bone–patellar tendon–bone anterior cruciate ligament reconstruction were randomly assigned to 2 groups. The first group received a ropivacaine continuous femoral nerve block and oral hydrocodone (block group). The second group received an intra-articular bupivacaine/morphine injection and oral oxycodone (injection group). Patients in both groups could receive intramuscular injection of hydromorphone for breakthrough pain; most patients in the block group also received bolus doses of ropivacaine through the femoral catheter. Subjects rated their worst, average, and current pain levels using a visual analog scale and category-ratio scale the morning after surgery. Postoperative narcotic pain medication use was converted to morphine-equivalent doses. Results Postoperative pain ratings did not differ between the treatment groups. The largest difference in pain ratings between the groups was 0.5 cm for worst pain level (P = .345). Total narcotic use did not differ significantly between groups (1.1 morphine equivalent doses in both groups; P = .671). Conclusions Continuous femoral block with ropivacaine appeared to have no clinical advantage in the immediate postoperative period after anterior cruciate ligament reconstruction when compared with an intra-articular injection of bupivacaine/morphine. Both methods are effective for pain control after anterior cruciate ligament reconstruction.

Paper 21: The Effect of Preemptive Pudendal Nerve Blockade on Postoperative Pain Following Pelvic Reconstructive Surgery: A Prospective Randomized Double-Blind Placebo-Controlled Trial

OBJECTIVE: The role of preemptive analgesia in relieving pain following transvaginal pelvic reconstructive surgery has not yet been investigated. We aimed to assess the effect of preemptive pudendal nerve blockade on pain and consumption of narcotic analgesia following transvaginal pelvic reconstructive surgery. METHODS: This was a prospective, randomized, double blind, placebo-controlled trial. Patients undergoing transvaginal pelvic reconstructive surgery under general anesthesia were randomized to receive pudendal block with either bupivacaine 0.25% or placebo (normal saline 0.9%) immediately before surgery. All surgeries were performed transvaginally, under general anesthesia induced by intravenous fentanyl 2μg/kg and propofol 2mg/kg. All patients received postoperative intravenous hydromorphone patient controlled analgesia. Patients were asked to report on their pain intensity 1, 3, 5, 7, 18 and 24 hours postoperatively, using a validated visual analogue pain scale from 0–10. Analgesic requirements were consistently recorded at 3, 7, 18 and 24 hours after surgery. Main outcome measures included postoperative pain severity, and hydromorphone consumption. RESULTS: One hundred and ten patients enrolled in the study, of which 106 were randomized, and 102 received preemptive pudendal block analgesia, 51 with bupivacaine 0.25% and 51 with normal saline. The 2 patient groups did not differ in baseline demographic and clinical characteristics, surgical procedures, anesthetic dose, total blood loss, operative time, surgical and medical complications. There were no significant differences between the 2 groups in mean postoperative pain scores (1 hour: 4.63 vs. 4.80; 3 hours: 3.71 vs. 3.87; 5 hours: 2.89 vs. 3.10; 7 hours: 2.85 vs. 3.12; 18 hours: 3.22 vs. 3.47; 24 hours: 3.23 vs. 3.12), and consumption of intravenous hydromorphone (0–3 hours: 1.84 vs. 1.77 mg; 4–7 hours: 1.19 vs. 1.20 mg; 8–18 hours: 2.89 vs. 2.35 mg). Additional boluses of hydromorphone (18% vs. 18%) and ketoralac (12% vs. 8%), as well as mean oral hydrocodone (10.6 vs. 12.7mg) and ibuprofen (630 vs. 762 mg) consumption in the first 24 hours after surgery were not significantly different between the two groups. There were no significant differences in mean total hospital stay between the 2 patient groups (39.6 vs. 37.3 hours). There were no complications directly related to the pudendal nerve blockade in any of the study patients. CONCLUSIONS: Preemptive pudendal nerve blockade does not affect postoperative pain intensity or the consumption of narcotic analgesia following pelvic reconstructive surgery.

Remifentanil infusion facilitates early recovery for obese outpatients undergoing laparoscopic cholecystectomy.

D espite the well known adverse effects of obesity, it is still the most common nutritional disorder in the United States. Unfortunately, there is a paucity of data supporting the use of one anesthetic technique over another in obese (versus nonobese) patient populations. Prolonged emergence time from general anesthesia in obese patients can be problematic in the ambulatory setting because it can delay the early recovery process. Cork et al. (1) reported that the use of IV anesthetic and analgesic drugs does not guarantee a shorter emergence period in the obese population. Because remifentanil can reduce the required endtidal concentration of volatile anesthetics by up to 50% (2,3), we hypothesized that the use of a remifentanil infusion during a sevoflurane-based anesthetic would facilitate emergence from anesthesia in obese patients undergoing ambulatory surgery.

Effect of preincision versus postincision infiltration with bupivacaine on postoperative pain

Study Objective: To compare the efficacy of preincision wound infiltration with bupivacaine to wound infiltration at the end of the operation. Design: A prospective, randomized, double-blind study. Setting: University medical center. Patients: 56 ASA status I and II women scheduled for abdominal hysterectomy were randomly assigned to one of three treatment groups. Interventions: Group 1 (control) received no local anesthetic infiltration. Group 2 received subcutaneous infiltration with 40 ml of bupivacaine 0.5% (pH 6.9) 15 minutes prior to incision. Group 3 received wound infiltration with a similar solution at the end of surgery. Anesthesia was induced with thiopental 3.0 mg/kg IV, droperidol 50 μg/kg IV, and sufentanil 0.5 μg/kg IV, and maintained with nitrous oxide 67% in oxygen and sufentanil 0.1 μg/kg IV boluses as required. Postoperative pain was treated with morphine via a patient-controlled analgesia delivery system for 24 hours, followed by oral hydrocodone for 3 days. Measurements and Main Results: The opioid consumption was recorded for 4 days postoperatively. Pain scores were measured at 4 to 8-hour intervals using 100 mm visual analog scales. There was no difference in either the opioid analgesic requirements or the pain scores between the three study groups. Conclusions: Wound infiltration, either preincision or postincision, had no clinically significant effect on the pain scores or analgesic requirements following abdominal hysterectomy.

Spontaneous pneumothorax in early pregnancy: Successful management by thoracoscopy

Spontaneous pneumothorax in early pregnancy: Successful management by thoracoscopy