Alfentanil versus fentanyl for emergency department rapid sequence induction with ketamine: A-FAKT, a pilot randomized trial.

BACKGROUND: Fentanyl is often administered during rapid sequence induction of anesthesia (RSI) in the emergency department (ED) to ameliorate the hypertensive response that may occur. Due to its more rapid onset, the use of alfentanil may be more consistent with both the onset time of the sedative and the commencement of laryngoscopy. As such, we compared the effect of alfentanil and fentanyl on post-induction hemodynamic changes when administered as part of a standardized induction regimen including ketamine and rocuronium in ED RSI. METHODS: This was a double-blind pilot randomized controlled trial of adult patients requiring RSI in the ED of three urban Australian hospitals. Patients were randomized to receive either alfentanil or fentanyl in addition to ketamine and rocuronium for RSI. Non-invasive blood pressure and heart rate were measured immediately before and at two, four, and six minutes after induction. The primary outcome was the occurrence of at least one post-induction systolic blood pressure outside the pre-specified range of 100-160mmHg (with adjustment for patients with baseline hypertension). Secondary outcomes included hypertension, hypotension, hypoxia, first-pass intubation success, 30-day mortality, and the pattern of hemodynamic changes. RESULTS: A total of 61 patients were included in the final analysis (31 in the alfentanil group and 30 in the fentanyl group). The primary outcome was met in 58% of the alfentanil group and 50% of the fentanyl group (difference 8%, 95% confidence interval: -17% to 33%). The 30-day mortality rate, first-pass success rate, and incidences of hypertension, hypotension, and hypoxia were similar between the groups. There were no significant differences in systolic blood pressure or heart rate between the groups at any of the measured time-points. CONCLUSION: Alfentanil and fentanyl produced comparable post-induction hemodynamic changes when used as adjuncts to ketamine in ED RSI. Future studies could consider comparing different dosages of these opioids.

Respiratory Effects of the Atypical Tricyclic Antidepressant Tianeptine in Human Models of Opioid-induced Respiratory Depression.

BACKGROUND: Animal data suggest that the antidepressant and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor modulator tianeptine is able to prevent opioid-induced respiratory depression. The hypothesis was that oral or intravenous tianeptine can effectively prevent or counteract opioid-induced respiratory depression in humans. METHODS: Healthy male and female volunteers participated in two studies that had a randomized, double blind, placebo-controlled, crossover design. First, oral tianeptine (37.5-, 50-, and 100-mg doses with 8 subjects) pretreatment followed by induction of alfentanil-induced respiratory depression (alfentanil target concentration, 100 ng/ml) was tested. Primary endpoint was ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg (V̇E55). Next, the ability of four subsequent and increasing infusions of intravenous tianeptine (target tianeptine plasma concentrations 400, 1,000, 1,500, and 2,000 ng/ml, each given over 15 min) to counteract remifentanil-induced respiratory depression was determined in 15 volunteers. Ventilation was measured at isohypercpania (baseline ventilation 20 ± 2 l/min). The primary endpoint was minute ventilation during the 60 min of tianeptine versus placebo infusion. RESULTS: Alfentanil reduced V̇E55 to 13.7 (95% CI, 8.6 to 18.8) l/min after placebo pretreatment and to 17.9 (10.2 to 25.7) l/min after 50-mg tianeptine pretreatment (mean difference between treatments 4.2 (-11.5 to 3.0) l/min, P = 0.070). Intravenous tianeptine in the measured concentration range of 500 to 2,000 ng/ml did not stimulate ventilation but instead worsened remifentanil-induced respiratory depression: tianeptine, 9.6 ± 0.8 l/min versus placebo 15.0 ± 0.9 l/min; mean difference, 5.3 l/min; 95% CI, 2.5 to 8.2 l/min; P = 0.001, after 1 h of treatment. CONCLUSIONS: Neither oral nor intravenous tianeptine were respiratory stimulants. Intravenous tianeptine over the concentration range of 500 to 2000 ng/ml worsened respiratory depression induced by remifentanil.

Time interval between alfentanil and rocuronium administration necessary to prevent rocuronium-induced withdrawal movement.

BACKGROUND: We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (TimeAR50). METHODS: A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 µg/mL. Then, alfentanil 15 µg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon's up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection. RESULTS: The TimeAR50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the TimeAR50 was 4.7 s (95% confidence interval [CI], 1.2-7.6 s) and 20.3 s (95% CI, 7.7-26.1 s) in the male and female patients, respectively. The TimeAR95 was 10.6 s (95% CI, 7.7-25.3 s) and 35.0 s (95% CI, 28.1-95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups. CONCLUSION: The TimeAR50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL: http://www.chictr.org.cn . Registry number: ChiCTR2100045137 ) .

Oxycodone versus other opioid analgesics after laparoscopic surgery: a meta-analysis.

BACKGROUND: Intravenous opioids are administered for the management of visceral pain after laparoscopic surgery. Whether oxycodone has advantages over other opioids in the treatment of visceral pain is not yet clear. METHODS: In this study, the analgesic efficiency and adverse events of oxycodone and other opioids, including alfentanil, sufentanil, fentanyl, and morphine, in treating post-laparoscopic surgery visceral pain were evaluated. This review was conducted according to the methodological standards described in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. The PubMed, Embase, and Cochrane databases were searched in December 2019. RESULTS: Ten studies were included in this review. The sample size was 695 participants. The results showed that compared with morphine and fentanyl, oxycodone had a more potent analgesic efficacy on the first day after laparoscopic surgery, especially during the first 0.5 h. There was no significant difference in sedation between the two groups. Compared to morphine and fentanyl, oxycodone was more likely to lead to dizziness and drowsiness. Overall, patient satisfaction did not differ significantly between oxycodone and other opioids. CONCLUSIONS: Oxycodone is superior to other analgesics within 24 h after laparoscopic surgery, but its adverse effects should be carefully considered.

Sedation with alfentanil versus fentanyl in patients receiving extracorporeal membrane oxygenation: outcomes from a single-centre retrospective study.

INTRODUCTION: In November 2016, our institution switched from alfentanil to fentanyl for analgesia and sedation in adult patients receiving extracorporeal membrane oxygenation. There is no published evidence comparing the use of alfentanil with fentanyl for sedation in extracorporeal membrane oxygenation patients. We conducted a retrospective observational study to explore any significant differences in patient outcomes or in the prescribing of adjunct sedatives before and after the switch. METHODS: Patients were retrospectively identified from a prospectively recorded database of all patients who received extracorporeal membrane oxygenation at our institution between January 2016 and October 2017. Patients included those sedated with alfentanil or fentanyl. The total daily doses of intravenous opioids (alfentanil or fentanyl) were calculated for each patient, and the prescribing of adjunctive sedative or analgesic agents was recorded. Patient demographics, extracorporeal membrane oxygenation modality, clinical outcomes including mortality and length of intensive care and hospital stay were recorded. RESULTS: A total of 174 patients were identified, 69 on alfentanil and 95 on fentanyl. There was no difference found between groups for mode of extracorporeal membrane oxygenation, age, Acute Physiology and Chronic Health Evaluation 2 score (APACHE II) and Charlson score, except for body mass index (p = 0.002). No differences in patient outcomes was observed between groups, although patients in the alfentanil group received a significantly higher median total daily dose of adjuvant sedatives (quetiapine (p = 0.016) and midazolam (p = 0.009)). CONCLUSIONS: No differences in patient outcomes were found between extracorporeal membrane oxygenation patients sedated with alfentanil compared with fentanyl. There was a statistically significant reduction in some adjunctive sedatives in patients managed with a fentanyl-based regimen. Prospective studies are required to confirm these results.

Previously published drug interaction models predict loss of response for transoesophageal echocardiography sedation well but not response to oesophageal instrumentation.

Response surface models (RSMs) were used to predict effects of multiple drugs interactions. Our study was aimed to validate accuracy of the previous published volunteer models during transoesophageal echocardiography (TEE). This is a cross-sectional study with 20 patients scheduled for transesophageal echocardiography in Taipei Veterans General Hospital, Taiwan. Effect-site concentration pairs of alfentanil and propofol were recorded and converted to equivalent remifentanil and propofol effect-site concentrations. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed every 2 minutes. Using these data, previous published models of loss of response (LOR), intolerable ventilatory depression (IVD), and loss of response to esophageal instrumentation (LREI) were then estimated. Accuracy of prediction is assessed by calculating the difference between the true response and the model-predicted probability. Clinical events such as interruption of TEE were recorded. The average procedure time was 11 minutes. Accuracy for prediction of LOR and LREI is 63.6% and 38.5%, respectively. There were four patients experienced desaturation for less than 1 minute, which were not predicted by IVD model, and one interruption of TEE due to involuntary movement. The previous published drug-interaction RSMs predict LOR well but not LREI for TEE sedation. Further studies using response surface methodology are needed to improve quality for TEE sedation and clinical implementation.

Trends in the medical supply of fentanyl and fentanyl analogues: United States, 2006 to 2017.

Fentanyl is an important opioid for pain management, but also has exceptional potential for misuse. Seven states have implemented opioid prescribing laws. The objectives of this study were to: 1) characterize the temporal pattern of fentanyl, fentanyl analogue, and other opioid use over the past decade, and 2) determine whether opioid prescribing laws impacted fentanyl use in the US. Drug weights were obtained from the US Automated Reports of Consolidated Orders System (June 2018), a comprehensive publically available resource, from 2006 to 2017 for fentanyl, sufentanil, remifentanil, alfentanil, other prescription opioids, and analyzed by presence of a state opioid prescribing law. Fentanyl, corrected for population, was reduced from 2016 to 2017 (-17.9%) and these decreases significantly exceeded the changes in hydrocodone (-12.3%), oxycodone (-10.1%), morphine (-13.3%), or codeine (-8.8%). Fentanyl showed a particularly large decline in Maine, a state with a strong opioid prescribing law. There was a 3.5 fold difference in fentanyl (µg per capita) in Alaska (488.2) relative to Oregon (1718.4). Hospital use of remifentanil and sufentanil tripled from 2006 to 2017. Although all states experienced a 2016 to 2017 decline in fentanyl, and this reduction was larger than many other prescription opioids, the rate of decline varied over three-fold between states. Strong state laws may account for a portion of the variance in fentanyl and other opioid reductions. The population health risks of fentanyl and fentanyl analogues warrants ongoing vigilance.

Systematic review of anaesthetic medication for ERCP based on a network meta-analysis.

AIMS: We performed a systematic review of various anaesthetic medications for endoscopic retrograde cholangiopancreatography (ERCP) and aimed to make a comprehensive comparison based on a network meta-analysis. METHODS: We searched globally recognized electronic databases, including PubMed, Cochrane Central and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of anaesthetic medications for ERCP. Network meta-analysis was conducted by evaluating the procedure time, adverse effects and drug requirements. The cumulative probability P value was utilized to rank the medications under examination. RESULTS: Seventeen RCTs that examined 1877 patients were included in this research. Under good convergence and efficiency, data analysis was performed using a consistency model. For the comparison of procedure times, we found that a combination of dexmedetomidine and ketamine (P = 0.19) or propofol plus pethidine (P = 0.18) seemed to be the two best medications for reducing procedure time. Additionally, midazolam combined with dexmedetomidine plus pethidine seemed to be the safest application for ERCP (P = 0.36). Propofol plus alfentanil also exhibited a good safety value (P = 0.28). For evaluation of drug requirements, the whole network connection could not be established; thus, comparisons in two subgroups were conducted. The results showed that midazolam combined with dexmedetomidine plus pethidine (P = 0.41) and propofol plus refentanil (P = 0.94) were superior to others in decreasing drug requirements. CONCLUSIONS: Based on the objective results and our conclusions, we deemed that a combination of midazolam and dexmedetomidine was recommended, and propofol plus opioids also revealed great clinical value. However, we are still expecting more clinical research in the future.

Effect of Intravenous Alfentanil on Nonpainful Thermally Induced Hyperalgesia in Healthy Volunteers.

Experimental interventions that activate specific components of clinical pain are necessary for characterization of underlying mechanisms and pharmacology. Cutaneous hyperalgesia has been described that uses nonpainful heat to induce secondary hyperalgesia. This study evaluated the effect of intravenous alfentanil on experimental cutaneous hyperalgesia created using this method. Eighteen subjects participated in a randomized, double-blinded, placebo-controlled crossover study consisting of 2 sessions, 1 with alfentanil and 1 with placebo. Using a computer-controlled infusion pump, alfentanil or matching placebo was maintained at a constant plasma level of 75 ng/mL for 1 hour followed by the application of a 40°C heat stimulus to the right thenar eminence for 15 minutes. The temperature was raised by 1°C every 15 minutes until the subject reported pain or 45°C was reached. After the end point was reached, the temperature was maintained, and repeat testing was performed. The nonpainful heat created an area of secondary cutaneous hyperalgesia and significant decrease in mechanical pain threshold on heat-treated right vs untreated left during placebo administration. Alfentanil prevented the hypersensitivity when compared to placebo (P < .05) but failed to reduce the area of secondary hyperalgesia created by nonpainful heat when compared to placebo (P = .06). Neither alfentanil nor the heat lamp treatment showed any significant effect on other neurosensory measures. This study demonstrated a reliable production of cutaneous hyperalgesia using a nonpainful stimulus that is affected by the systemic delivery of alfentanil. This model for human cutaneous experimental pain may be a useful method for scientific characterization of analgesics.

Randomized clinical trial of propofol versus alfentanil for moderate procedural sedation in the emergency department.

STUDY OBJECTIVE: To compare the frequency of airway and respiratory adverse events leading to an intervention between moderate sedation using alfentanil or propofol. METHODS: We performed a randomized clinical trial in which adults undergoing moderate sedation in the ED received either alfentanil or propofol. Our primary outcome was the frequency of airway and respiratory adverse events leading to an intervention. Other outcomes included sedation depth, efficacy, sedation time, patient satisfaction, pain, and satisfaction. RESULTS: 108 subjects completed the trial: 52 receiving alfentanil and 56 receiving propofol. Airway or respiratory adverse events leading to an intervention were similar between the two groups: 23% for alfentanil and 20% for propofol (p=0.657). There were no serious adverse events in any group. Secondary outcomes were notably different in the rate of reported pain (48% for alfentanil, 13% for propofol) and recall (75% for alfentanil, 23% for propofol) and similar in the rate of satisfaction with the procedure (87% for alfentanil, 84% for propofol). CONCLUSION: We found a similar frequency of airway and respiratory adverse events leading to intervention between alfentanil and propofol used for moderate procedural sedation. Both agents appear safe for moderate procedural sedation.

Synergistic antinociceptive effects of alfentanil and propofol in the formalin test.

The present study was conducted to determine the combined analgesic effect of alfentanil and propofol in the formalin test. Diluted formalin was injected into the dorsal surface of the right hind paw in rats. Nociceptive behavior was determined by counting the number of flinches of the injected paw for 1 h after injection; a reduction in formalin­induced flinching was interpreted as an antinociceptive effect. Isobolographic analysis was used to determine the type of antinociceptive interaction (additivity, antagonism or synergism). Extracellular signal­regulated kinase (ERK) and c­fos protein levels were also detected by western blot analysis to determine the potential mechanisms of the synergistic effect. Alfentanil, propofol or an alfentanil­propofol combination had an antinociceptive effect in the formalin test. The median effective dose (ED50), value of the individual drug was also obtained. The derived theoretical ED50 for the antinociceptive effect (4.36 mg/kg) was different from the observed experimental ED50 value (2.51 mg/kg). The interaction between alfentanil and propofol that produced the antinociceptive effect was synergistic according to isobolographic analysis. Furthermore, the combination of alfentanil and propofol treatments may produce synergistically antinociceptive effects by inhibiting the phosphorylation of ERK1/2 and decreasing the expression of c­fos in the spinal cord. These results demonstrated that combined treatment, with alfentanil and propofol, produced synergistic antinociceptive effects in the formalin test and may have therapeutic potential for the treatment of acute pain.

Feasibility of monomodal analgesia with IV alfentanil during burn dressing changes at bedside (in spontaneously breathing non-intubated patients).

INTRODUCTION: The severe pain related to repeated burn dressing changes at bedside is often difficult to manage. However these dressings can be performed at bedside on spontaneously breathing non-intubated patients using powerful intravenous opioids with a quick onset and a short duration of action such as alfentanil. The purpose of this study is to demonstrate the efficacy and safety of the protocol which is used in our burn unit for pain control during burn dressing changes. PATIENTS AND METHODS: Cohort study began after favorable opinion from local ethic committee has been collected. Patient's informed consent was collected. No fasting was required. Vital signs for patients were continuously monitored (non-invasive blood pressure, ECG monitoring, cutaneous oxygen saturation, respiratory rate) all over the process. Boluses of 500 (±250) mcg IV alfentanil were administered. A continuous infusion was added in case of insufficient analgesia. Adverse reactions were collected and pain intensity was measured throughout the dressing using a ten step verbal rating scale (VRS) ranging from 0 (no pain) to 10 (worst pain conceivable). RESULTS: 100 dressings (35 patients) were analyzed. Median age was 45 years and median burned area 10%. We observed 3 blood pressure drops, 5 oxygen desaturations (treated with stimulation without the necessity of ventilatory support) and one episode of nausea. Most of the patients (87%) were totally conscious during the dressing and 13% were awakened by verbal stimulation. Median total dose of alfentanil used was 2000µg for a median duration of 35min. Pain scores during the procedure were low or moderate (VRS mean=2.0 and maximal VRS=5). Median satisfaction collected 2h after the dressing was 10 on a ten step scale. CONCLUSION: Pain control with intravenous alfentanil alone is efficient and appears safe for most burn bedside repeated dressings in hospitalized patients. It achieves satisfactory analgesia during and after the procedure. It is now our standard analgesic method to provide repeated bedside dressings changes for burned patients.

Sedoanalgesia for cardioversion: comparison of alfentanil, remifentanil and fentanyl combined with propofol and midazolam: a prospective, randomized, double-blind study.

OBJECTIVE: Electrical cardioversion (EC) is a short but painful procedure to restore sinus rhythm. The aim of this study is to compare the effect of fentanyl, remifentanil and alfentanil in association with propofol and midazolam for elective EC. PATIENTS AND METHODS: Ninety-nine patients older than 18-years, American Society of Anesthesiologists I/II/III grades undergoing elective EC were randomized into 3 groups. All patients received 2 mg midazolam and propofol (0.5 mg/kg). Group A received alfentanil (5 µg/kg i.v. bolus), Group F received fentanyl (0.5 µg/kg i.v. bolus) and Group R received remifentanil (0.25 µg/kg i.v. bolus). Hemodynamics and respiratory variables [Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), SpO2, respiratory rate (RR)], and Modified Aldrete recovery score (MARS) were assessed at six different time points (baseline, right after EC, and 3rd min, 5th min, 10th min, 30th min following EC). Also, induction times (time to reach RSS to 5) and recovery times (time to reach MARS to 8) were recorded. The incidence of respiratory depression, bradycardia, hypotension and adverse effects were also recorded. RESULTS: Hemodynamic variables were similar in all groups. SpO2 values in Group R were significantly lower at 3rd min (p = 0.005). Induction and recovery times were longest in Group F. There were significant differences at 3rd, 5th and 10th minute MARS values between groups. The incidence of hypotension and bradycardia were similar in all groups (p > 0.05) but respiratory depression was higher in Group R (p = 0.047). CONCLUSIONS: Propofol alfentanil combination has more beneficial advantages in their rapid onset, early recovery time and less respiratory depression than remifentanil and fentanyl.

Propofol-alfentanyl versus midazolam-alfentanyl in inducing procedural amnesia of upper gastrointestinal endoscopy in children--blind randomised trial.

UNLABELLED: In paediatric patients, esophagogastroduodenoscopy (EGD) is commonly performed with the use of sedation. The aim of the study was to compare the effectiveness of propofol and midazolam in providing procedural amnesia and controlling behaviour in children undergoing diagnostic EGD. Children (9-16 years), classified to the first or second class of the American Society of Anaesthesiologists' physical status classification referred for EGD, were randomly assigned to receive propofol with alfentanyl or midazolam with alfentanyl for sedation during the procedure. Within 120 min after the procedure, patients were repeatedly investigated for memory of the procedure and for memory of pain intensity during EGD with the use of the visual analogue scale. Activity and cooperation of the patient during the procedure was assessed with the relative adequacy scale. Of the 51 children, 48 completed the study. Propofol was significantly better than midazolam in inducing amnesia of procedural pain (mean difference 11.53 mm; 95 % confidence interval [CI] 0.96 to 22.10), loss of memory of the procedure (relative risk 0.4; 95 % CI 0.21 to 0.59) and controlling behaviour (relative risk 2.12; 95 % CI 1.33 to 3.36). CONCLUSION: In children sedated for EGD, propofol is significantly better than midazolam at providing procedural amnesia and controlling behaviour during the procedure.

A web-based survey of United Kingdom sedation practice in the intensive care unit.

PURPOSE: The purpose of this work was to obtain a detailed perspective of sedation practice. Sedation included sedative and opioid choice, presence of local guidelines, and use of scoring systems. METHODS: A Web-based survey was designed. The aim was to gain sufficient detail of UK sedation while also being succinct enough to complete in 15 minutes. It was composed of relevant demographics, policy, sedative choice, and analgesia. The survey was piloted before launch. The investigators selected the intensive care unit (ICU) pharmacist as the respondent. RESULTS: One hundred fifty-seven ICUs responded. Eighty-nine (59%) reported use of sedation guidelines, 78% undertook sedation holds, and 87% use sedation scores. Only 42% used a daily sedation target. Seventy (43%) assess for delirium; 27 of those use a validated tool. Propofol (89%) use was common, followed by midazolam (49%). Morphine (49%), fentanyl (34%), and alfentanil (34%) were the most frequently used opioids. CONCLUSION: This survey confirmed expected variation in UK sedation practice. Recognized strategies such as target sedation score and sedation policy are underused. A 43% uptake in delirium screening suggests that larger engagement is required to meet national standards.

Effect of ketamine versus alfentanil following midazolam in preventing emergence agitation in children after sevoflurane anaesthesia: a prospective randomized clinical trial.

OBJECTIVE: To investigate the effect of intranasal ketamine versus alfentanil in addition to oral midazolam for the prevention of emergence agitation in children. METHODS: Children undergoing urological surgery with sevoflurane anaesthesia received oral midazolam 40 min before induction and were then randomly assigned to receive 2 mg/kg ketamine, 10 µg/kg alfentanil or 1 ml isotonic saline intranasally. Parental separation status and mask acceptance were assessed preoperatively. Emergence agitation was evaluated using a paediatric anaesthesia emergence delirium (PAED) score. RESULTS: Data from 78 children were evaluated in the study. There were no significant differences between the groups in demographic characteristics, recovery times or parental separation scores. Mask acceptance was significantly better in the ketamine group than in the saline group. The mean PAED score in the ketamine group was significantly better than in the other two groups, but was similar in the saline and alfentanil groups. The incidence of emergence agitation was 3.8%, 36.0% and 40.7% in the ketamine, alfentanil and saline groups, respectively. CONCLUSIONS: The addition of intranasal ketamine to oral midazolam significantly improved the quality of induction and reduced sevoflurane-induced emergence agitation, in children undergoing urological surgery.

Two studies on reversal of opioid-induced respiratory depression by BK-channel blocker GAL021 in human volunteers.

BACKGROUND: Opioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced respiratory depression in animals due to a stimulatory effect on ventilation at the carotid bodies. To assess in humans whether GAL021 stimulates breathing in established opioid-induced respiratory depression and to evaluate its safety, a proof-of-concept double-blind randomized controlled crossover study on isohypercapnic ventilation (study 1) and subsequent double-blind exploratory study on poikilocapnic ventilation and nonrespiratory end points (study 2) was performed. METHODS: In study 1, intravenous low- and high-dose GAL021 and placebo were administrated on top of low- and high-dose alfentanil-induced respiratory depression in 12 healthy male volunteers on two separate occasions. In study 2, the effect of GAL021/placebo on poikilocapnic ventilation, analgesia, and sedation were explored in eight male volunteers. Data are mean difference between GAL021 and placebo (95% CI). RESULTS: Study 1: Under isohypercapnic conditions, a separation between GAL021 and placebo on minute ventilation was observed by 6.1 (3.6 to 8.6) l/min (P < 0.01) and 3.6 (1.5 to 5.7) l/min (P < 0.01) at low-dose alfentanil plus high-dose GAL021 and high-dose-alfentanil plus high-dose GAL021, respectively. Study 2: Similar observations were made on poikilocapnic ventilation and arterial pCO2. GAL021 had no effect on alfentanil-induced sedation, antinociception and no safety issues or hemodynamic effects became apparent. CONCLUSION: GAL021 produces respiratory stimulatory effects during opioid-induced respiratory depression with containment of opioid-analgesia and without any further increase of sedation. Further studies are needed to confirm these preliminary data.

Methadone and oedema in the palliative care setting: a case report and review of the literature.

INTRODUCTION: Methadone is a synthetic opioid which is being used with increased frequency in the palliative care setting for management of complex pain. There have been cases published reporting the development of oedema with methadone maintenance therapy but no cases on the association with methadone and peripheral oedema in the palliative care setting. As yet, the underlying mechanisms are unclear. CASE PRESENTATION: This case report describes a gentleman with ependymoma and difficult-to-control lower back pain and scrotal pain. This pain had failed to respond to other strong opioids. He was prescribed methadone and then subsequently developed bilateral peripheral oedema. CASE MANAGEMENT: Peripheral oedema resolved following cessation of methadone. CONCLUSIONS: This highlights an important potential adverse effect of methadone in a society of increased methadone prescription for pain control. The published literature to date is reviewed and possible underlying mechanisms explored.