A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

AIMS: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. METHODS: Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5 mg dose of nalbuphine nasal spray vs. 10 mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. RESULTS: Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6 = 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset = 0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia = 5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. CONCLUSION: Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

Optimal Post-Operative Nalbuphine Dose Regimen: A Randomized Controlled Trial in Patients with Laparoscopic Cholecystectomy.

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

Nalbuphine reduces the incidence of emergence agitation in children undergoing Adenotonsillectomy: A prospective, randomized, double-blind, multicenter study.

OBJECTIVE: To evaluate the effect of nalbuphine on emergence agitation (EA) in children undergoing adenotonsillectomy. DESIGN: Multicenter, prospective, double-blind, randomized controlled trial. SETTING: The First People's Hospital of Foshan and three other participating institutions in China, from April 2020 to December 2021. PATIENTS: Eight hundred patients, 3-9 years of age, American Society of Anesthesiologists (ASA) classification I or II, undergoing elective adenotonsillectomy were included. INTERVENTIONS: Nalbuphine (0.1 mg/kg) or saline was administered intravenously. MEASUREMENTS: The incidence of EA; the pediatric anesthesia emergence delirium (PAED) scale; and the faces, legs, activity, cry, and consolability (FLACC) scales. Extubation time, duration of post-anesthesia care unit (PACU) stay, anesthesia nurses' and parents' satisfaction, and other side effects. MAIN RESULTS: The incidence of EA in the nalbuphine group was lower than that in the saline group 30 min after extubation (10.28% vs. 28.39%, P = 0.000). In addition, the FLACC scores in the nalbuphine group were lower than those in the saline group 30 min after extubation (P < 0.05). Furthermore, the proportion of moderate-to-severe pain cases (FLACC scores >3) was significantly lower in the nalbuphine group than in the saline group (33.58% vs. 60.05%, P = 0.000). Adjusting the imbalance of postoperative pain intensity, the risk of EA was still lower in the nalbuphine group at 0 min (OR, 0.39; 95% CI, 0.26-0.60; P = 0.000), (OR, odds ratio; CI, confidence interval), 10 min (OR, 0.39; 95% CI, 0.19-0.79; P = 0.01), and 20 min (OR, 0.27; 95% CI, 0.08-0.99; P = 0.046) than in the saline group. There were no significant differences in extubation time, duration of PACU stay, nausea and vomiting, or respiratory depression between the two groups (P > 0.05). CONCLUSION: Nalbuphine reduced the incidence of EA in children after adenotonsillectomy under general anesthesia, which may be involved in both analgesic and non-analgesic pathways.

Analgesic efficacy and safety of nalbuphine versus morphine for perioperative tumor ablation: a randomized, controlled, multicenter trial.

BACKGROUND: The study will compare the efficacy and safety of nalbuphine hydrochloride injection and morphine hydrochloride injection for perioperative analgesia in tumor ablation and the differences between the two groups regarding duration of surgery, average daily dose, patient satisfaction with analgesia, quality of life, and other indicators. Furthermore, it will evaluate the clinical application of nalbuphine and morphine for perioperative analgesia in ablation surgery and provides important reference and guidance for clinical practice. METHODS: This is a randomized controlled study. Patients who were diagnosed by clinicians and required tumor ablation are enrolled and randomized to the experimental groups. In the test group, nalbuphine 80 mg + 0.9% normal saline (72 ml) is set in the patient-controlled analgesia pump, which is connected 15 min before ablation under electrocardiogram monitoring and surgery is performed immediately. The doses are as follows: initial,: 0.15 ml/kg,; background:, 0.5 ml/h,; compression:, 2 ml,; and lockout time:, 15 min. If the numeric rating scale is ≥ 4 points, the drug is administered by compression. The control group receives similar treatment under similar conditions as the test group except morphine (80 mg) is administered instead of nalbuphine (80 mg). The primary endpoints are the effective rate of analgesia and the incidence of adverse reactions (nausea and vomiting, dizziness, itching, constipation, hypoxemia, and urinary retention); the secondary endpoints are pain intensity, satisfaction with analgesia, duration of surgery, postoperative hospital stay, average daily dose, uninterrupted completion rate of surgery without complaints of pain, quality of life assessment, and vital signs. DISCUSSION: This study, to the best of our knowledge, is the first randomized controlled trial of nalbuphine patient-controlled analgesia in ablation surgery. TRIAL REGISTRATION: U.S. Clinical Trials Network Registration No.: NCT05073744 . Registered on 11 October, 2021.

Effects of multimodal analgesia of flurbiprofen axetil, nalbuphine and patient controlled intravenous analgesia on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery.

To evaluate the efficacy of multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and patient controlled intravenous analgesia (PCIA) on inflammatory factor levels and stress response in patients after laparoscopic radical gynecological malignancy surgery. The data of 100 patients admitted to our hospital from May 2019 to May 2020 for laparoscopic radical gynecological malignancy surgery were retrospectively analyzed and they were assigned (1:1) to either an experimental group or a control group according to the alphabetical order of their initials. The experimental group was given preemptive analgesia with flurbiprofen axetil, postoperative analgesia with nalbuphine hydrochloride, and PCIA and the control group was given conventional analgesic measures. The pain scores at 1h, 6h, 12h, 24h and 48h postoperatively in the experimental group were remarkably lower than those in the control group (P<0.001). The experimental group showed significantly lower inflammatory factor levels, pain mediator levels and stress response indexes in the morning before surgery, 1d, and 2d after surgery than the control group (P<0.001). The multimodal analgesia of flurbiprofen axetil, nalbuphine hydrochloride and PCIA can effectively alleviate the stress response and inflammatory response in patients after radical gynecologic malignancy surgery and the patients' pain perception is reduced with a high safety profile.

Pain management after ambulatory surgery: a prospective, multicenter, randomized, double-blinded parallel controlled trial comparing nalbuphine and tramadol.

BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study.

The outcome of relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) in adults is poor, with less than 20% of patients surviving at 5 years. Nelarabine is the only drug specifically approved for R/R T-ALL/T-LBL, but the information to support its use is based on limited available data. The aim of this observational phase four study was to provide recent additional data on the efficacy and safety of nelarabine in adults with R/R T-ALL/T-LBL and to evaluate the feasibility and outcome of allogeneic hematopoietic stem cell transplant (SCT) after salvage with nelarabine therapy. The primary endpoints were overall response rate (ORR) and overall survival (OS). Additional endpoints were safety, SCT rate and post-SCT OS. Between May 2007 and November 2018, 118 patients received nelarabine salvage therapy at 27 Italian hematology sites. The median age was 37 years (range 18-74 years), 73% were male, 77 had a diagnosis of T-ALL and 41 of T-LBL, and 65/118 (55%) had received more than two lines of therapy. The median number of nelarabine cycles was two (range 1-4); 43/118 (36%) patients had complete remission (CR), 16 had partial remission (14%) and 59 (50%) were refractory, with an ORR of 50%. The probability of OS, from the first dose of nelarabine, was 37% at 1 year with a median survival of 8 months. The OS at 1 year was significantly better for the 47 patients (40%) who underwent SCT after nelarabine salvage therapy (58% vs 22%, log-rank P < .001). The probability of OS at 2 and 5 years from SCT was 46% and 38%, respectively. Seventy-five patients (64%) experienced one or more drug-related adverse events (AE). Grade III-IV neurologic toxicities were observed in 9/118 (8%) of cases and thrombocytopenia or/and neutropenia (grade III-IV) were reported in 41% and 43% of cases, respectively. In conclusion, this is one of the largest cohorts of adult patients with R/R T-ALL/T-LBL treated in real life with nelarabine. Taking into account the poor prognosis of this patient population, nelarabine represents an effective option with an ORR of 50% and a CR rate of 36%. In addition, 40% of cases following nelarabine salvage therapy could undergo SCT with an expected OS at 2 and 5 years of 46% and 38%, respectively. The safety profile of nelarabine was acceptable with only 8% of cases showing grade III-IV neurological AE.

Postsurgery analgesic and sedative drug use in a French neonatal intensive care unit: A single-center retrospective cohort study.

OBJECTIVE: To describe pain assessment, the pattern of analgesic and sedative drug use, and adverse drug reactions in a neonatal intensive care unit (NICU) during the postsurgery phase. METHOD: Demographic characteristics, pain scores, and drug use were extracted and analyzed from electronic patient medical files for infants after surgery, admitted consecutively between January 2012 and June 2013. RESULT: One hundred and sixty-eight infants were included. Acute (DAN score) and prolonged (EDIN score) pain assessment scores were used in 79% and 64% of infants, respectively, on the 1st day. This percentage decreased over the 7 days following surgery. The weekly average scores postsurgery were 2/15 (±2.2) for the EDIN score and 1.6/10 (±2.0) for the DAN score. The rates of pain control were 88% for the EDIN and 72% for the DAN. The most prescribed opiate drug was fentanyl (98 patients; 58%) with an average dose of 1.8 (±0.6) µg/kg/h. Midazolam was used in 95 patients (56%), with an average dose of 35 (±14) µg/kg/h. A bolus was administered in 7% (±7.4) of the total dose for fentanyl and 8% (±9.3) for midazolam. Similar doses were used in term and preterm neonates. Of 118 patients receiving fentanyl and/or midazolam, 40% presented urinary retention, 28% a weaning syndrome. Paracetamol (155 patients; 92%) and nalbuphine (55 patients; 33%) were the other medications most often prescribed. CONCLUSION: The off-label use of fentanyl and midazolam was necessary to treat pain after surgery. Pain assessment should be conducted for all neonates in order to optimize their treatment. Research on analgesic and sedative medicine in vulnerable neonates seems necessary to standardize practices and reduce adverse drug reactions.

Comparing efficacy and safety between Naldebain® and intravenous patient-controlled analgesia with fentanyl for pain management post-laparotomy: study protocol for a randomized controlled, non-inferior trial.

BACKGROUND: A long-acting prodrug of nalbuphine, nalbuphine sebacate, has been developed for meeting the unmet medical need of long-acting analgesics. Naldebain® (nalbuphine sebacate) has been developed as a new premedication for postoperative pain management. The primary objective of this study is to determine the efficacy and safety of a single dose of intramuscular Naldebain® in patients scheduled to undergo elective laparotomy. METHODS/DESIGN: A total of 110 patients will be recruited and randomized into two treatment groups. Group 1 receives a single dose of Naldebain® intramuscularly 24 ± 12 h prior to surgery. Group 2 receives intravenous patient-controlled analgesia (PCA) with fentanyl through 48 h postsurgery. Both groups will have follow-up observations until the final visit (day of discharge, day 6-30). The primary efficacy endpoint is to assess time-specific pain intensity calculated as the area under the curve (AUC) of a visual analog scale at individual time points and by using total AUC. Safety endpoints-including incidence of treatment, emergent adverse events, and percentage of abnormality from baseline to final visit-in vital signs, laboratory tests, and injection site evaluations will also be analyzed. Statistical analyses will be performed on the data to compare the two groups. DISCUSSION: Post-laparotomy pain can have a harmful effect on patient recovery; therefore, a slow-release formulation that can cover at least 7 days of analgesic effect is required. This study will demonstrate whether a single use of Naldebain® is not less efficacious than PCA with fentanyl for pain management as a non-inferior trial. TRIAL REGISTRATION: NCT03296488 .

Non-anesthesiologist-administered Propofol is not Related to an Increase in Transcutaneous CO2 Pressure During Flexible Bronchoscopy Compared to Guideline-based Sedation: A Randomized Controlled Trial.

INTRODUCTION: Evidence for the use of non-anesthesiologist-administered propofol for sedation during flexible bronchoscopy is scarce. The main objective of this study was to determine whether non-anesthesiologist-administered propofol balanced sedation was related to higher transcutaneous CO2 pressure compared with current guideline-based sedation (combination midazolam and opioid). Secondary outcomes were post-procedural recuperation time, patient satisfaction and frequency of adverse events. METHODS: In this randomized controlled trial we included data from outpatients aged 18 years or older with an indication for flexible bronchoscopy in a university hospital in northern Mexico. RESULTS: Ninety-one patients were included: 42 in the midazolam group and 49 in the propofol group. During 60min of transcutaneous capnometry monitoring, mean transcutaneous CO2 pressure values did not differ significantly between groups (43.6 [7.5] vs. 45.6 [9.6]mmHg, P=.281). Propofol was related with a high Aldrete score at 5, 10, and 15min after flexible bronchoscopy (9 [IQR 6-10] vs. 10 [9,10], P=.006; 9 [8-10] vs. 10 [IQR 10-10], P<.001 and 10 [IQR 9-10] vs. 10 [10], respectively) and with high patient satisfaction on a visual analogue scale of 1 (not satisfied) to 10 (very satisfied) (8.41 [1.25] vs. 8.97 [0.98], P=.03). Frequency of adverse events was similar among groups (30.9% vs. 22.4%, P=.47). CONCLUSION: Compared with guideline-recommended sedation, non-anesthesiologist-administered propofol balanced sedation is not associated with higher transcutaneous CO2 pressure or with more frequent adverse effects. Propofol use is associated with faster sedation recovery and with high patient satisfaction. CLINICAL TRIAL REGISTRATION: NCT02820051.

Sebacoyl Dinalbuphine Ester Extended-release Injection for Long-acting Analgesia: A Multicenter, Randomized, Double-Blind, And Placebo-controlled Study in Hemorrhoidectomy Patients.

OBJECTIVES: This study was conducted to evaluate the safety and efficacy of single sebacoyl dinalbuphine ester (SDE) injection (150 mg/2 mL) when administered intramuscularly to patients who underwent hemorrhoidectomy for postoperative long-acting analgesia. METHODS: A total of 221 patients scheduled for hemorrhoidectomy from 6 centers in Taiwan were randomly divided into SDE group and placebo group, and received the treatment, vehicle or SDE, 1 day before the surgery. Visual analogue scale (VAS) was recorded up to 7 to 10 days. Pain intensity using VAS AUC through 48 hours after surgery was calculated as the primary efficacy endpoint. RESULTS: Area under the curve of VAS pain intensity scores (VAS AUC) through 48 hours after hemorrhoidectomy was significantly less in SDE group than those in placebo group (209.93 vs. 253.53). VAS AUC from the end of surgical procedure to day 7 was also significantly different between SDE and placebo group (630.79 vs. 749.94). SDE group consumed significantly less amount of other analgesics, such as PCA ketorolac and oral ketorolac. Median time from the end of surgery to the first use of pain relief medication was also shortened in the placebo group than in the SDE group. Most adverse events were assessed as mild and tolerable in both groups. DISCUSSION: SDE injection demonstrated an extended analgesia effect, with a statistically significant reduction in pain intensity through 48 hours and 7 days after hemorrhoidectomy.

Nalbuphine for postoperative pain treatment in children.

BACKGROUND: Several surveys over the past few years have demonstrated that postoperative pain in children is not treated appropriately. One pharmacological treatment option in a multimodal approach for postoperative pain treatment is the systemic administration of opioids. However, opioids are rarely used for postoperative pain treatment in children due to fear of adverse events. One long-standing opioid for systemic use is nalbuphine, a kappa-receptor agonist and µ-receptor antagonist. The efficacy of nalbuphine is believed to be similar to morphine. Increased dosing might result in a ceiling effect, and thus less analgesia than expected. In addition, there might be a lower risk for opioid-induced side effects (nausea, vomiting) and severe adverse events (respiratory depression) due to the antagonistic effect of the µ-receptor. Nalbuphine may be an useful opioid for postoperative use in children, but exact efficacy (e.g. compared to other commonly used opioids) has not been determined yet. OBJECTIVES: To assess the efficacy and adverse events of nalbuphine for acute postoperative pain treatment in children undergoing surgery. SEARCH METHODS: We systematically searched the following databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 7), MEDLINE via Pubmed (January 1966 to July 2013) and EMBASE via Ovid (January 1947 to July 2013). We did not impose any restrictions regarding language or publication date. We checked all reference lists of retrieved articles for additional references. SELECTION CRITERIA: All randomised controlled trials (RCTs) investigating nalbuphine compared with placebo or other opioids were included. DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the retrieved articles and made a decision regarding inclusion or exclusion of studies for this review. The same authors also performed the data extraction and the assessment of risk of bias. MAIN RESULTS: Ten RCTs including 658 patients were finally included in this systematic review. Five trials compared nalbuphine with placebo. Data from one out of five studies for the outcome moderate/severe pain following nalbuphine compared to placebo gave a risk ratio (RR) 1 hour postoperatively (postop) of 0.1 (95% confidence interval (CI) 0.01 to 0.71; low quality evidence) and a RR 2 hours postop of 0.14 (95% CI 0.02 to 1.06; low quality evidence). The estimated RR based on data from a single study indicated that nalbuphine reduced the requirement for analgesia two hours postop (RR 0.47; 95% CI 0.27 to 0.84; low quality evidence). Two included trials compared nalbuphine with morphine and showed a nonsignificant lower or comparable RR for moderate/severe pain at 1 hour postop (RR 0.84; 95% CI 0.12 to 5.74; low quality evidence), and 2 hours postop (RR 1.09; 95% CI 0.59 to 2.01; low quality evidence) for nalbuphine versus morphine. Four trials compared nalbuphine with tramadol for postoperative pain; data from one trial (per outcome) revealed a lower but nonsignificant RR for the need of additional rescue analgesics in children receiving nalbuphine (RR 2 hours postop 0.75; 95% CI 0.39 to 1.43; low quality evidence) (RR 12 hours postop 0.33; 95% CI 0.04 to 2.77; low quality evidence). One out of three trials comparing nalbuphine with pethidine demonstrated that the RR was not significantly lower following nalbuphine administration compared to pethidine (RR 2 hours postop 1.07; 95% CI 0.52 to 2.23; low quality evidence) (RR 24 hours postop 1.13; 95% CI 0.52 to 2.44; very low quality evidence). The most common adverse event was postoperative nausea and vomiting (PONV). Only one included trial reported that the RR for PONV in the postoperative care unit (PACU) was not significantly higher following nalbuphine compared to placebo (RR 1.00; 95% CI 0.16 to 6.42; low quality evidence) nor to morphine (RR 1.33; 95% CI 0.64 to 2.77; low quality evidence). AUTHORS' CONCLUSIONS: Because the overall quality of available evidence was low, this systematic review could not definitively show that the analgesic efficacy of nalbuphine is superior compared to placebo. Furthermore, due to the lack of significant results the comparison with other common opioids is also unclear. The same holds true for the evidence focusing on adverse events following nalbuphine compared to placebo or other opioid administration. The evidence is limited, because studies did not report conclusively all important postoperative pain outcomes (e.g. number of patients with the need for rescue analgesia, postoperative pain scores). Thus, a quantitative analysis was not possible for many major aspects (e.g. rescue analgesia, pain scores) and heterogeneity could not be further explored.

Hemodynamic effects of dexmedetomidine--fentanyl vs. nalbuphine--propofol in plastic surgery.

UNLABELLED: Dexmedetomidine has demonstrated to be useful in several clinical fields due to its respiratory safety and cardiovascular stability. We undertook this study to determine its usefulness in plastic surgery. Sixty patients were divided into two parallel groups. A group received dexmedetomidine--fentanyl and the comparison group received nalbuphine--propofol, both with same dose of midazolam. Blood pressure, heart rate and oxygen saturation were determined during the preoperative, intraoperative and recuperation periods. RESULTS: In both groups, hemodynamic constants decreased intraoperatively. Dexmedetomidine--fentanyl decreased more than in the nalbuphine--propofol (systolic blood pressure, p = 0.006; diastolic blood pressure, p = 0.01 and heart rate, p = 0.007). Comparatively, oxygen saturation was greater in the dexmedetomidine--fentanyl group vs. nalbuphine--propofol (p = 0.0001). Recovery time for the nalbuphine--propofol group was shorter than in the dexmedetomidine--fentanyl group (p = 0.0001). CONCLUSIONS: Dexmedetomidine shows the same cardiovascular stability but with absence of respiratory depression.

Predictive factors of PACU stay after herniorraphy in infant: a classification and regression tree analysis.

INTRODUCTION: Herniorraphy is a common surgical intervention in infants, particularly in those born prematurely. Prematurity and perioperative sedation have been shown to be risk factors for postoperative apnea. However, their influence upon PACU stay duration has not been evaluated. The goal of this study was to investigate predictive factors for PACU stay in infants undergoing herniorraphy. MATERIAL AND METHODS: This study is a retrospective analysis of perioperative data in infants <6 months of age undergoing herniorraphy during the period November 2007-November 2009. Collected data included age, gestational age at birth, post-conceptional age, weight, weight at birth, type of anesthesia (spinal vs general), perioperative administration of opioids and paracetamol, duration of surgery, duration of PACU stay, and apnea in PACU. Data analysis used classification and regression trees (CART) with a 10-fold cross-validation. RESULTS: Two hundred and ninety-six patients were included in the analysis. Five parameters were found to predict the duration of PACU stay: a post-conceptional age below 45 weeks, prematurity, general anesthesia, postoperative opioid administration, and the use of intraoperative regional analgesia. CRT method allows constructing a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross-validation were 79.7% and 76.6%, respectively. DISCUSSION: Our study allows construction of an accurate predictive tree for PACU stay during herniorraphy in infants <6 months. Parameters found to influence the duration of PACU stay were related to anesthesia techniques and perinatal outcomes.

The impact of parenteral narcotic choice in the development of acute chest syndrome in sickle cell disease.

BACKGROUND: Acute chest syndrome (ACS) represents a serious morbidity and often fatal complication in patients with sickle cell disease. Painful episodes which require hospitalization are most often treated with opioids, which may then influence the development of ACS. Nalbuphine is a parenteral opioid which effectively treats pain and may cause less ACS. PROCEDURE: This retrospective chart review documented 988 admissions for painful episodes at 2 institutions and recorded the incidence of ACS and opioid used. RESULTS: At the Children's Hospital in St Louis, Missouri, the incidence of ACS in patients treated with morphine alone was 10.8% versus at the Children's Mercy Hospital in Kansas City, Missouri, the incidence was 2.1% for patients treated solely with nalbuphine. CONCLUSIONS: When nalbuphine is used alone as the single parenteral opioid agent to treat painful episodes in patients with sickle cell disease, the incidence of ACS is less than when compared with other opioids used to treat pain.

[Intrathecal opioid medication for perioperative analgesia in severely handicapped children undergoing spinal operations]. / Intrathekale Opioidmedikation zur perioperativen Analgesie bei schwer behinderten Kindern mit Wirbelsäulenoperationen.

PURPOSE OF THE STUDY: Intrathecal opioids have been shown to be safe and effective for postoperative analgesia in healthy children for spinal surgery. The aim of this study was to evaluate the applicability of intrathecal opioids in severely handicapped children scheduled for spinal surgery. METHODS: With hospital ethical committee approval, patients with physical states III and IV of the ASA classification requiring spinal surgery were retrospectively studied. In addition to inhalational anesthesia with sevoflurane or intravenous anesthesia using propofol, morphine 20 microg/kgBW and sufentanil 1.5 microg/kgBW were administered intrathecally before surgery. After surgery an infusion of nalbuphine was started. Need for additional intraoperative and postoperative analgesics, time of extubation, postoperative pain scores and p(a)CO2 values as well as adverse effects were recorded. RESULTS: A total of 28 patients aged from 2.8 to 18.5 years (median 11.6 years) were studied. Immediate tracheal extubation in the operating room was possible in 17 patients and for 11 patients delayed extubation was elected. All patients were extubated within 24 h except for 1 patient who received massive postoperative transfusions. In 26 out of 28 patients (93%) the combination of intrathecal opioids with postoperative nalbuphine provided adequate analgesia. Observed side effects were post-operative nausea and vomiting (PONV), pruritus and moderate hypoventilation. In two patients a change to intravenous morphine therapy was necessary. CONCLUSION: The use of intrathecal opioids for perioperative pain control from spinal fusion in severely handicapped children is feasible. Intrathecal opioids provide adequate postoperative analgesia and allow early extubation without persisting relevant respiratory compromise in most of these patients.

Combination of low-dose nalbuphine and morphine in patient-controlled analgesia decreases incidence of opioid-related side effects.

BACKGROUND/PURPOSE: The addition of ultra-low-dose naloxone to patient-controlled analgesia (PCA) with morphine reduces opioid-related side effects. Nalbuphine, a mixed opioid agonist-antagonist, may be able to attenuate opioid-related side effects. The goal of the present study was to investigate the effect of combined low-dose nalbuphine and morphine in PCA for postoperative pain control after gynecological surgery. METHODS: This randomized, double-blind, controlled study enrolled 174 female patients who were undergoing total abdominal hysterectomy, myomectomy, or ovarian tumor excision. In the control group, the PCA formula was 1 mg/mL pure morphine. In the study group, the PCA formula was 1 mg/mL morphine and 10 microg/mL nalbuphine (1:100). Numerical rating score, PCA requirement, nausea, vomiting, use of antiemetics, pruritus, use of antipruritics, and opioid-related adverse events were investigated at 1, 2, 4, and 24 hours postoperatively. RESULTS: One hundred and sixty-nine patients completed the study: 86 in the control group and 83 in the study group. The incidence of nausea was lower in the study group (41%) than in the control group (65%). The incidence of vomiting, use of antiemetics, pruritus, and use of antipruritics did not differ between the two groups. The numerical rating pain score and PCA requirements were not significantly different between the two groups. CONCLUSION: Combination of low-dose nalbuphine and morphine in PCA decreases the incidence of opioid-related nausea, without affecting the analgesia and PCA requirement. This novel combination can improve the quality of PCA used for postoperative pain control after gynecological surgery.

Combination of opioid agonist and agonist-antagonist: patient-controlled analgesia requirement and adverse events among different-ratio morphine and nalbuphine admixtures for postoperative pain.

BACKGROUND: Nalbuphine, a mixed agonist-antagonist opioid, has a potential to attenuate the mu-opioid effects and to enhance the kappa-opioid effects. However, when morphine and nalbuphine are mixed together, the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown. METHODS: This randomized, double-blind controlled study investigated five different combining ratios of morphine and nalbuphine in 311 patients undergoing gynaecologic operations. The concentrations [morphine (mg ml(-1))]/[nalbuphine (mg ml(-1))] were 1/0 in Group 1, 0.75/0.25 (ratio 1:3) in Group 2, 0.5/0.5 (ratio 1:1) in Group 3, 0.25/0.75 (ratio 3:1) in Group 4, and 0/1 in Group 5. Patient-controlled analgesia (PCA) requirement, postoperative pain, and adverse events were evaluated throughout the postoperative 24 h period. RESULTS: Twenty-four hour PCA requirements were similar among the five groups. Verbal rating scores for pain were statistically higher in Groups 2 and 4 than in Group 3. The incidences of pruritus were higher in Group 1 (15.6%) than in Group 2 (6.2%), Group 3 (3.4%), Group 4 (1.6%), and Group 5 (0%). The incidences and severity of dizziness, nausea, and vomiting were not significantly different. CONCLUSIONS: The interaction between morphine and nalbuphine in PCA admixture on analgesia is additive. Combinations of morphine and nalbuphine in PCA can decrease the incidence of pruritus, and the antipruritus effect is ratio-dependent. This may provide a novel combination strategy of opioid agonist and agonist-antagonist for postoperative pain management after gynaecologic surgery.