Alfentanyl (R39209): initial clinical experience with a new narcotic analgesic

R39209 (Alfentanyl), a new narcotic analgesic with a uniquely short duration of effect, was used to supplement nitrous oxide and oxygen for the maintenance of anaesthesia. Twenty-two patients undergoing minor surgery were studied. Clinical anaesthesia was excellent or good in most (16) of the patients, and recovery was excellent or good in 18 patients, waking time being less than one minute in 15 patients. However the incidence of complications and side-effects, mainly movement, apnoea, difficulty in assisting ventilation, nausea and vomiting was high. Intravenous administration of R39209 during anaesthesia induced significant depression of respiratory rate and minute volume during the second, third and fourth minutes after injection. There was an unexplained significant rise in respiratory rate and minute volume in the first 30 seconds after the first injection. The first administration of R39209 also caused an unexplained, significant reduction in cardiac rate. An insignificant rise in mean systolic blood pressure followed injection of the drug. The transient effect of R39209 was confirmed in clinical practice, and the drug exhibited the features of a typical narcotic analgesic. It is concluded that R39209 will have a useful place in anaesthetic practice, and that better clinical results will be obtained with more experience of the drug, and better selection of indications for its use.     

Plasma morphine levels produced by continuous infusion in children

Blood samples were taken from six children aged between 10 months and 15 years, at intervals over a period of 40 hours while they were receiving continuous morphine infusions. The plasma morphine values obtained showed similar and consistent levels 15-30 minutes after starting the infusions.     

Postoperative On-Demand Analgesie mit Pentazocin (Fortral)

Zusammenfassung Das Verfahren der On-Demand Analgesie (intravenöse Selbstapplikation von Analgetica) wurde im Rahmen der postoperativen Schmerztherapie bei 40 ASA I-III Patienten nach elektiven Eingriffen erprobt. Bei Bedarf konnten über einen Handdruckknopf Einzelboli von Pentazocin (8 mg) bis zu einer Stundenmaximaldosis von 60 mg angefordert werden, die von einer Mikroprozessor-kontrollierten Infusionspumpe (On-Demand Analgesia Computer, ODAC) geliefert wurden. Zwischen zwei gültigen Anfragen lag eine Geräte-Refraktärzeit von jeweils einer Minute. Zur Vermeidung von Katheterverstopfungen wurden kleine Pentazocinmengen (1 mg/h) unabhängig vom jeweiligen Bedarf kontinuierlich infundiert. Die Behandlungsdauer betrug 20,3 ± 5,9 h (Mittelwert, St. Abw.); bei einer mittleren Anforderungshäufigkeit von 20,0 ± 12,7 Demands pro Patient ergab sich ein Pentazocinverbrauch von 135,6 ± 81,4 g/kg/h. Die Selbstapplikation war durch ausgeprägte inter- und intraindividuelle Variationen gekennzeichnet. Patienten nach abdominalchirurgischen Eingriffen unterschieden sich weder im Pentazocinkonsum noch in der erreichten Schmerzlinderung signifikant von solchen nach orthopädischen Operationen. Zwischen den Geschlechtern ergaben sich ebenfalls keine statistisch signifikanten Unterschiede. Ein eindeutiger Einfluß der Narkosetechnik (Neuroleptanalgesie, Halothan- oder lumbale Spinalanaesthesie) auf die Analgeticaanforderungen ließ sich nicht feststellen. Wirksamkeit und Patientenakzeptanz erschienen ausgezeichnet: 68% der Kranken beurteilten die Effektivität der On-Demand-Analgesie als besser als die einer früher erlebten konventionellen Schmerztherapie. Ins Gewicht fallende Nebenwirkungen wurden nicht beobachtet; am häufigsten waren Übelkeit, Erbrechen oder Schwitzen zu verzeichnen.

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Patient-controlled analgesia with pentazocine for the treatment of postoperative pain

Summary Patient-controlled analgesia (PCA, intravenous self-application of narcotics) was studied during the early postoperative period. Subjects were 40 ASA I-III patients recovering from elective major and minor surgery (each 20 having undergone abdominal or orthopaedic operations). Pentazocine bolusses of each 8 mg were available via a hand-button whenever the patients felt pain relief necessary, and delivered by a microprocessor-controlled injection pump (On-Demand Analgesia Computer, ODAC). Hourly maximum dose was set to 60 mg with a pump refractory time of 1 min between valid demands. A continuous low-dose pentazocine infusion (1 mg/h) was additionally administered in order to prevent catheter obstruction. Duration of the PCA period was 20.3 ± 5.9 h (mean, standard deviation). During this time, 20.0 ± 12.7 demands per patient were recorded resulting in mean pentazocine consumption of 135.6±81.4 g/kg/h. Self-administration was characterized by considerable intra- and interindividual variability. There were no statistically significant differences with regard of pentazocine consumption or pain relief between abdominal and orthopaedic patients, nor could any be demonstrated between the sexes. Similarly, no clear differences were found after various anaesthetic techniques (neuroleptanalgesia, halothane or spinal anaesthesia). Over-all efficacy and patient acceptance proved to be excellent. Effectiveness of PCA was judged superior by about 68% of patients when compared with previously experienced conventional postoperative analgesia. Side effects (nausea, emesis, sweating) occurred in about 10–18 % but were usually of minor intensity. Circulatory or respiratory problems were not observed during the PCA period. Patient-controlled analgesia is discussed as a promising concept for the treatment of acute pain and clinical pain research.

     

Is outpatient laparoscopic cholecystectomy wise?

The authors report a prospective analysis of their experience with 506 consecutive laparoscopic cholecystectomies to examine the appropriatenss of outpatient or same-day laparoscopic cholecystectomy. Thirty-eight patients experienced at least one postoperative complication. The complication was clinically evident or suspected in only 4 of these 38 patients within 8 h following surgery. Thirty-nine percent and 76% of complications were clinically detected at 24 and 48 h, respectively. Nausea and vomiting occurred among 32% of all patients on the day of operation and extended into the 1st postoperative day in 10%. Compared to predicted values, forced vital capacity was 61±5% 1 h postoperatively in 32 patients studied. At 6 and 24 h postoperatively, forced vital capacity was 63±7% and 66±7% respectively. Postoperative analgesic medication requirement was determined in 220 patients who were provided with a patient-controlled intravenous morphine analgesia machine with no basal rate. Consumption of morphine was highly variable but substantial on the day of operation: 17±16 mg. Most complications of laparoscopic cholecystectomy, including life-threatening complications, are not apparent by 8 h postoperatively and may not be apparent at 24 h. The potential for delay in the diagnosis and treatment of complications, variable but substantial analgesic requirements, impaired postoperative ventilation, and postoperative gastrointestinal dysfunction argue for the need to use great caution in selecting patients for outpatient laparoscopic cholecystectomy. Criteria are proposed to identify patients who are safest for outpatient laparoscopic cholecystectomy.     

麻醉镇痛药物对Oddi括约肌运动功能影响的研究

目的 经胆道镜Oddi括约肌测压,观察常规剂量的吗啡、度冷丁、强痛定及曲吗多对Oddi括约肌运动功能的影响。方法 胆道术后留有T型管病人70例,随机分为吗啡组、度冷丁组、强痛定组及曲吗多组,测量用药前后的十二指肠压(DP)、Oddi括约肌基础压(SOBP)、收缩波幅(SOCA)、收缩频率(SOF)、收缩间期(SOD)及胆总管压(CBDP)。结果 肌注吗啡及强痛定后SOBP和SOCA升高,SOF增快,吗啡组CBDP升高(P<0.05);肌注度冷丁后各指标无明显变化;肌注曲吗多后SOBP和SOCA明显降低(P<0.05);应用各药物后收缩间期无明显变化。结论 常规剂量的吗啡及强痛定对Oddi括约肌起激动作用,常规剂量的度冷丁对Oddi括约肌无明显作用,常规剂量的曲吗多对Oddi括约肌具有抑制作用。     

Skin pretreatment with an Er:YAG laser promotes the transdermal delivery of three narcotic analgesics

Because of their low oral bioavailabilities and short half-lives, it may be more feasible to administer narcotic analgesics via the skin. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The aim of this study was to enhance the transdermal delivery of three narcotic drugs, including morphine, nalbuphine, and buprenorphine, with an erbium:yttrium–aluminum–garnet (Er:YAG) laser pretreatment. In an in vitro pig skin permeation experiment, Er:YAG laser pretreatment of the skin produced a 10~35-fold enhancement in drug permeation that was dependent on the laser fluence and the narcotic analgesic used. The permeation of morphine and nalbuphine showed higher enhancement with Er:YAG laser treatment as compared to that of buprenorphine. This may have been due to the higher lipophilicity and molecular mass of buprenorphine than the other two narcotic drugs. A photomechanical wave was generated by filtering laser radiation through a polystyrene target. The experimental results showed that a single photomechanical wave was sufficient to enhance morphine permeation by sevenfold. This enhancement was significantly lower than that produced by direct laser irradiation, indicating the predominant mechanism of SC ablation by the Er:YAG laser for transdermal drug delivery.     

吗啡耐受和依赖时第二信使分子和阿片受体变化及与谷氨酸受体的关系

目的　研究吗啡耐受和依赖时某些第二信使分子和阿片受体变化及与谷氨酸受体的关系。方法　竞争性蛋白结合法、共聚焦显微镜技术和受体结合实验检测 c AMP水平、胞内钙和阿片受体变化。结果　在表达诱导型一氧化氮合酶 c DNA神经细胞中 ,吗啡急性刺激剂量依赖性抑制 c AMP生成 ,慢性用药引起 c AMP代偿性增加。谷氨酸受体拮抗剂 MK80 1增强吗啡的急性抑制效应 ,抑制阿片受体介导 c AMP系统脱敏。对吗啡慢性给药细胞 ,用吗啡刺激和纳络酮戒断引起 [Ca2 ]i增加 ,阿片受体 Kd值增加和 Bmax值减少 ,MK80 1对这些指标的改变没有影响。结论　 MK80 1减轻阿片耐受和依赖的机制可能不是改变阿片受体特性 ,主要与受体后信号转导有关。     

Combined preemptive and preventive analgesia in morbidly obese patients undergoing open gastric bypass: A pilot study

PURPOSE: It is difficult to balance adequate pain control against the risk of sedation and depressed breathing in severely obese patients. This study assesses the effects of combined preemptive and preventive analgesia on narcotic use after open gastric bypass. METHODS: Twenty patients were randomized in this prospective double-blind trial comparing preoperative 30 mg intravenous ketorolac (Toradol), 0.25% subcutaneous bupivacaine (Marcaine) with epinephrine along the planned incision, and 0.25% bupivacaine in the rectus fascia before closing with identical injections with 0.9% saline. The patients' self-assessed pain on a visual analogue scale (VAS) and total narcotic use by patient-controlled analgesia (PCA) and rescue medication were recorded. RESULTS: Age, body mass index (BMI), incision length, and operative times were similar between the two groups, as was the average length of hospital stay (2.9 days). Self-reported pain was less in the treatment group 1 hour postoperatively (P = .01). Narcotic use was less in the treatment group during the first 2 hospital days (51% less on day 1 vs 44.5% less on day 2). Total narcotic use during the hospital stay was reduced by 40% (P = .02). CONCLUSIONS: Patients receiving combined preemptive and preventive analgesia used significantly less narcotic pain medication than the patients receiving placebo. The effect lasted beyond the duration of action of the local anesthetic.     

Does preoperative narcotic use adversely affect outcomes and complications after spinal deformity surgery? A comparison of nonnarcotic- with narcotic-using groups

Background contextThe role of preoperative (preop) narcotic use and its influence on outcomes after spinal deformity surgery are unknown. It is important to determine which patient factors and comorbidities can affect the success of spinal deformity surgery, a challenging surgery with high rates of complications at baseline.PurposeTo evaluate if preop narcotic use persists after spinal deformity surgery and whether the outcomes are adversely affected by preop narcotic use.Study design/settingRetrospective evaluation of prospectively collected data.Patient sampleTwo hundred fifty-three adult patients (230 females/23 males) undergoing primary spinal deformity surgery were enrolled from 2000 to 2009.Outcome measuresPreoperative and postoperative (postop) narcotic use and changes in Oswestry Disability Index (ODI), Scoliosis Research Society (SRS) pain, and SRS total scores.MethodsPreoperative, 2-year postop, and latest follow-up pain medication use were collected along with ODI, SRS pain, and SRS scores. Preoperative insurance status, surgical and hospitalization demographics, and complications were collected. All patients had a minimum 2-year follow-up (average 47.4 months).ResultsOne hundred sixty-eight nonnarcotic (NoNarc) patients were taking no pain meds or only nonsteroidal anti-inflammatories preoperatively. Eighty-five patients were taking mild/moderate/heavy narcotics before surgery. The average age was 48.2 years for the NoNarc group versus 53.6 years for the Narc group (p<.005). There were significantly more patients with degenerative than adult scoliosis in the Narc group (47 vs. 28, p<.001; mild 19 vs. 24, p<.02; moderate 6 vs. 14, p<.0003; heavy 3 vs. 10, p<.0002). Insurance status (private/Medicare/Medicaid) was similar between the groups (p=.39). At latest follow-up, 137/156 (88%) prior NoNarc patients were still not taking narcotics whereas 48/79 (61%) prior narcotic patients were now off narcotics (p<.001). Significant postop improvements were seen in Narc versus NoNarc groups with regard to ODI (26–15 vs. 44–30.3, p<.001), SRS pain (3.36–3.9 vs. 2.3–3.38, p<.001), and overall SRS outcome (3.36–4 vs. 2.78–3.68, p<.001) scores. A comparison of change in outcome scores between the two groups showed a higher improvement in SRS pain scores for the Narc versus NoNarc group (p<.001).ConclusionsIn adults with degenerative scoliosis taking narcotics a significant decrease in pain medication use was noted after surgery. All outcome scores significantly improved postop in both groups. However, the Narc group had significantly greater improvements in SRS pain scores versus the NoNarc group.     

Postoperative patient-controlled analgesia with sufentanil: analgesic efficacy and minimum effective concentrations

Sufentanil has so far seldom been used for intravenous postoperative patient-controlled analgesia (PCA), and the resulting serum concentrations have not yet been determined. Forty ASA I-III patients recovering from major gynecological operations were investigated to evaluate analgesic efficacy, side effects, patient acceptance and threshold concentrations of sufentanil in serum during the early postoperative period, using the On-Demand Analgesia Computer (ODAC). Following an individualized intravenous loading dose of 19.1 +/- 35.7 micrograms (mean +/- 1 s.d.), sufentanil demand doses were 6 micrograms with a concurrent infusion of 1.15 micrograms/h and a maximum hourly dose of 40 micrograms/h; the lockout time was set to 1 min. The duration of PCA was 17.3 +/- 2.1 h. During this time 16 +/- 11 demands per patient were recorded, resulting in an average sufentanil consumption of 131.1 +/- 69.4 micrograms or 7.5 +/- 3.7 micrograms/h (including loading dose). analgesia was mostly judged good. Side effects were only of minor intensity. Sufentanil proved to be about 2.2 to 3.8 times as potent an analgesic as fentanyl when both analgesic effect and duration were considered. Minimum effective sufentanil serum concentration (MEC) as determined by radioimmunoassay varied greatly and could be best described by a log-normal distribution (range less than 0.01-0.56 ng/ml, median 0.024 ng/ml). Intraindividual MEC variability was slightly lower than intersubject variability (76.0 vs. 84.8%). It is concluded that sufentanil is suitable for postoperative PCA. To get into the therapeutic window for analgesia, a serum sufentanil concentration of more than 0.03 ng/ml seems to be necessary.