Sublingual sufentanil tablet system for postoperative analgesia after gynecological surgery.

BACKGROUND: Gynecological procedures are among the most frequent surgical interventions, and effective postoperative analgesia is associated with improved patient comfort. Despite the efficacy of neuraxial analgesia, limitations and potential complications have led to seek new strategies for pain relief. A novel, pre-programmed, non-invasive, hand-held system (Sufentanil Sublingual Tablet System [SSTS]) displayed good results in the orthopedic setting. However, it has never been applied in gynecological procedures. METHODS: This retrospective observational case series evaluates receiving SSTS for postoperative analgesia. Data from 42 consecutive patients undergoing open gynecological surgery with Pfannenstiel incision were retrieved from medical charts in two Italian hospitals. RESULTS: The mean age was 49±11 years, and mean BMI was 24.4±4.6 kg/m2. We reported effective relief on both static and dynamic pain all along the perioperative period, with good effect on patient's rehabilitation. Postoperative nausea and vomiting is the most common adverse effect, but the incidence was strongly decreased with medical prophylaxis. SSTS was easy to prepare, use and manage by both patients and care providers. CONCLUSIONS: SSTS may be an interesting option for postoperative analgesia in gynecologic procedures. The efficacy in the management of dynamic pain is an interesting outcome that needs to be compared with the other standards of pain management, such as neuraxial techniques. Rigorous studies are required to give conclusive evidence, but this is the first report, to our knowledge, of SSTS use in open gynecologic procedures. Our preliminary experience encourages the routine application of SSTS in gynecologic surgery and will help designing future randomized controlled trials on the topic.

Effects of Deep Versus Moderate Neuromuscular Blockade in Laparoscopic Gynecologic Surgery on Postoperative Pain and Surgical Conditions: Protocol for a Randomized Controlled Trial.

BACKGROUND: Postoperative pain, especially shoulder pain, is commonly reported after laparoscopic gynecologic procedures. Some studies suggest that a lower insufflation pressure may reduce the risk of postoperative pain; however, there is no agreement on the optimal pneumoperitoneum pressure during gynecologic laparoscopic surgery or whether lower pressure would lead to clinically significant improvements without increasing operative complications. Questions remain regarding the clinical significance of improvements, safety, and cost-effectiveness of deep neuromuscular blockade with low-pressure pneumoperitoneum. OBJECTIVE: The primary objective of this study was to assess the superiority of anesthesia with deep neuromuscular blockade with pneumoperitoneum 8 mm Hg over moderate blockade with pneumoperitoneum 12 mm Hg in terms of overall pain 24 hours after surgery in adult women undergoing pelvic surgery for hysterectomy or benign adnexal diseases. Effects on the intensity and timing of postoperative pain in specific locations, surgeon satisfaction, respiratory and hemodynamic stability, operating times, and direct and indirect costs will be assessed. METHODS: In this multicenter, randomized controlled trial with a superiority design, 300 patients will be randomly allocated in the ratio 1:1 to moderate neuromuscular blockade with a target insufflation pressure of 12 mm Hg or deep neuromuscular blockade with a target insufflation pressure of 8 mm Hg, with stratification by type of surgery and clinical center. The patient, the statistician, and the nurse who will assess the primary endpoint will be blinded to the allocation. RESULTS: Recruitment to this trial is expected to open in June 2018 and is expected to close in June 2019. CONCLUSIONS: This study is designed to confirm the reported benefits of postoperative pain and provide additional data needed to address questions regarding the effects of this intervention on operating theater management and direct and indirect costs. Strengths of this protocol include the large sample size distributed among diverse institutions across the Italian territory and the collection and analysis of data on numerous secondary objectives. Limitations include the possible introduction of bias because the surgeon and anesthesiologist are not blinded to the intervention. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9277.

Activity-based costing analysis of the analgesic treatments used in postoperative pain management in Italy.

BACKGROUND: The aim of this analysis is to evaluate the costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in nine different Italian hospitals, defined as the cumulative cost of drugs, consumable materials and time required for anesthesiologists, surgeons and nurses to administer each analgesic technique. METHODS: Nine Italian hospitals have been involved in this study through the administration of a questionnaire aimed to acquire information about the Italian clinical practice in terms of analgesia. This study uses activity-based costing (ABC) analysis to identify, measure and give value to the resources required to provide the therapeutic treatment used in Italy to manage the postoperative pain patients face after surgery. A deterministic sensitivity analysis (DSA) has been performed to identify the cost determinants mainly affecting the final cost of each treatment analyzed. Costs have been reclassified according to three surgical macro-areas (abdominal, orthopedic and thoracic) with the aim to recognize the cost associated not only to the analgesic technique adopted but also to the type of surgery the patient faced before undergoing the analgesic pathway. RESULTS: Fifteen different analgesic techniques have been identified for the treatment of moderate to severe pain in patients who underwent a major abdominal, orthopedic or thoracic surgery. The cheapest treatment actually employed is the oral administration "around the clock" (€ 8.23), whilst the most expensive is continuous peripheral nerve block (€ 223.46). The intravenous patient-controlled analgesia costs € 277.63. In terms of resources absorbed, the non-continuous administration via bolus is the gold standard in terms of cost-related to the drugs used (€ 1.28), and when administered pro re nata it also absorbs the lowest amount of consumables (€0.58€) compared to all other therapies requiring a delivery device. The oral analgesic administration pro re nata is associated to the lowest cost in terms of health professionals involved (€ 6.25), whilst intravenous PCA is the most expensive one (€ 245.66), requiring a massive monitoring on the part of physicians and nurses. CONCLUSIONS: The analysis successfully collected information about costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in all the nine different Italian hospitals. The interview showed high heterogeneity in the treatment of moderate to severe pain after major abdominal, orthopedic and thoracic surgeries among responding anesthesiologists, with 15 different analgesic modalities reported. The majority of the analgesic techniques considered in the analysis is not recommended by any guideline and their application in real life can be one of the reasons for the high incidence of uncontrolled pain, which is still reported in the postoperative period. Health care costs have become more and more important, although the choice of the best analgesic treatment should be a compromise between efficacy and economic considerations.

Postoperative Takotsubo cardiomyopathy triggered by intraoperative fluid overload and acute hypertensive crisis.

The Takotsubo cardiomyopathy is a rare haemodynamic dysfunction, only recently reported perioperatively. While the diagnostic criteria have been established and the outcome is known as favorable, the pathophysiological mechanisms are not entirely understood. Here we present the case of a patient scheduled for laparoscopic hysterectomy and adnexectomy, who early postoperatively developed a Takotsubo cardiomyopathy supposedly triggered by an acute hypertensive crisis due to intraoperative fluid overload.

PAIN OUT: an international acute pain registry supporting clinicians in decision making and in quality improvement activities.

RATIONALE, AIMS AND OBJECTIVES: Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making. METHODS: PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery. RESULTS: The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM. CONCLUSION: PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.

Patients' perception of postoperative pain management: validation of the International Pain Outcomes (IPO) questionnaire.

UNLABELLED: PAIN OUT is a European Commission-funded project aiming at improving postoperative pain management. It combines a registry that can be useful for quality improvement and research using treatment and patient-reported outcome measures. The core of the project is a patient questionnaire-the International Pain Outcomes questionnaire-that comprises key patient-level outcomes of postoperative pain management, including pain intensity, physical and emotional functional interference, side effects, and perceptions of care. Its psychometric quality after translation and adaptation to European patients is the subject of this validation study. The questionnaire was administered to 9,727 patients in 10 languages in 8 European countries and Israel. Construct validity was assessed using factor analysis. Discriminant validity assessment used Mann-Whitney U tests to detect mean group differences between 2 surgical disciplines. Internal consistency reliability was calculated as Cronbach's alpha. Factor analysis resulted in a 3-factor structure explaining 53.6% of variance. Cronbach's alpha at overall scale level was high (.86), and for the 3 subscales was low, moderate, or high (range, .53-.89). Significant mean group differences between general and orthopedic surgery patients confirmed discriminant validity. The psychometric quality of the International Pain Outcomes questionnaire can be regarded as satisfactory. PERSPECTIVE: The International Pain Outcomes questionnaire provides an instrument for postoperative pain assessment and improvement of quality of care, which demonstrated good psychometric quality when translated into a variety of languages in a large European and Israeli patient population. This measure provides the basis for the first comprehensive postoperative pain registry in Europe and other countries.

Transdermal buprenorphine for postoperative pain control in gynecological surgery: a prospective randomized study.

OBJECTIVE: Although numerous methods are available for postoperative pain (POP) management, new approaches are constantly being investigated. This feasibility study assessed the buprenorphine transdermal therapeutic system (Bup-TTS) for the treatment of POP after gynecological open surgery. RESEARCH DESIGN AND METHODS: Forty-five patients were prospectively randomized to different Bup-TTS dosages (17.5, 35, or 52.5 µg/h). Patients were blinded with regard to patch dose. MAIN OUTCOME MEASURES: Efficacy was evaluated in terms of rescue boluses (intravenous morphine 2 mg in the first six postoperative hours, intravenous ketorolac 30 mg thereafter) required to achieve a static and dynamic Numerical Rating Scale (sNRS and dNRS) score ≤4. Side effects were evaluated from patch application (12 hours before surgery) until the 72nd postoperative hour. Patient satisfaction regarding POP management was assessed via anonymous questionnaire. RESULTS: All Bup-TTS groups required additional postoperative analgesia, particularly in the first postoperative hour. No between-group differences in sNRS/dNRS values were recorded at emergence from anesthesia. A significant inverse correlation occurred between Bup-TTS dosage and use of morphine (p = 0.04), ketorolac (p = 0.04) or both rescues (p = 0.02). Postoperative nausea/vomiting occurred in 3.1% of assessments, with no between-group differences and a significant correlation with morphine amount (p = 0.01). No serious side effects occurred. Despite no between-group difference, patient satisfaction was inversely correlated with the number of rescue doses (p < 0.001). Study limitations include the small sample size, the absence of a control group treated with a more conventional technique for POP relief, the focus on selected patients at low perioperative risk and the presence of slightly different types of open surgery (hysterectomy vs myomectomy only). CONCLUSION: Bup-TTS efficacy was directly proportional to its dosage, although additional analgesia was required, particularly in the first postoperative hour. Moreover, the consumption of morphine and ketorolac was inversely correlated to the Bup-TTS dosage. Increasing Bup-TTS doses were not associated with an increased incidence of side effects. Bup-TTS appears a safe and feasible approach for moderate POP management; further larger studies are warranted.

Pharmacokinetic considerations in the obese.

The steady rise in obesity observed in the recent years, coupled with its associated co-morbidities, suggests that clinicians will encounter obese patients with increasing frequency in their daily practice. Unfortunately, obese subjects are often excluded from clinical trials during the drug development process. Hence, the appropriate dose for obese patients is most often inferred from normal-weight subjects. Pharmacokinetic and pharmacodynamic variations induced by obesity are numerous and with profound clinical implications, particularly in anaesthesia and intensive care. This review provides a pragmatic approach to the pharmacokinetic considerations that should guide drug administration. We hereby offer a systematic approach to dosing scalars, followed by an analysis of the factors affecting pharmacokinetics in obesity, and provide a detailed discussion on the single most commonly used pharmacological agents in anaesthesia.

The effects of low-dose ephedrine on intubating conditions following low-dose priming with cisatracurium.

STUDY OBJECTIVE: To determine whether low-dose ephedrine plus priming with low-dose cisatracurium improves intubating conditions. DESIGN: Prospective, randomized, double-blinded study. SETTING: Operating room. PATIENTS: 124 ASA physical status I and II patients scheduled for elective surgery. INTERVENTIONS: Patients were randomly assigned to 4 groups (n = 31): Group PE (priming + ephedrine), Group P (priming), Group E (ephedrine), and Group NPE (no priming, no ephedrine). All patients were induced with propofol two mg/kg and sulfentanil 0.15 µg/kg. In the priming groups, 0.005 mg/kg (10% ED(95)) cisatracurium was given, followed three minutes later by 0.145 mg/kg of cisatracurium. In Groups E and NPE, a single dose of 0.15 mg/kg cisatracurium was given. Intravenous ephedrine 70 µg/kg was given in Groups PE and E. Tracheal intubation was attempted 60 seconds after the intubating dose of cisatracurium and was considered successful only if performed within 20 seconds. MEASUREMENTS: Intubating conditions were graded. Heart rate and non-invasive blood pressure, at one-minute intervals, were recorded during and 5 minutes after induction. MAIN RESULTS: The tracheas of all patients in Group PE were successfully intubated within 20 seconds versus 74% in Group P, 77% in Group E, and 64% in Group NPE (P < 0.001 vs. Group PE). Intubating conditions were graded good to excellent in all PE patients, but in only 52% of Groups P and E, and 48% of NPE patients (P < 0.001). Hemodynamic variables were comparable among groups (P = ns). CONCLUSIONS: Low-dose ephedrine plus priming with low-dose cisatracurium before an intubating dose, significantly improved clinical intubating conditions at 60 seconds.

Anesthesia and postoperative analgesia after intra-articular injection of warmed versus room-temperature levobupivacaine: a double-blind randomized trial.

PURPOSE: This prospective, randomized, blinded study was designed to compare the effects of warmed versus room-temperature levobupivacaine in patients undergoing knee arthroscopy and partial meniscectomy. METHODS: Patients were randomly allocated into 2 groups of 16 patients each. In all patients the 2 portal sites were infiltrated with 10 mL of room-temperature mepivacaine (20 mg/mL). In the first group, patients underwent intra-articular injection of 20 mL of levobupivacaine (5 mg/mL) and 0.005-mg/mL epinephrine (1:200,000) at a temperature of 40 degrees C +/- 0.2 degrees C, whereas in the second group the levobupivacaine and epinephrine were at room temperature (25 degrees C +/- 0.5 degrees C). Pain was graded and recorded intraoperatively and postoperatively by use of a visual analog scale (VAS). Analgesia was supplemented if the VAS score was 4 cm or greater with morphine intraoperatively or ketorolac postoperatively. RESULTS: There were no significant differences between groups in intraoperative and postoperative VAS values. There was no need for morphine as a rescue dose in any patient during surgery. Eight patients treated with warmed levobupivacaine and seven patients treated with room-temperature levobupivacaine requested a single rescue dose of ketorolac (30 mg) postoperatively. CONCLUSIONS: No compelling evidence exists to suggest that intra-articular injection of warmed levobupivacaine is more effective than room-temperature levobupivacaine for intraoperative anesthesia and postoperative analgesia in patients undergoing partial meniscectomy during knee arthroscopy. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Ultrasound-guided central venous cannulation in bariatric patients.

BACKGROUND: Central venous catheterization may be difficult in morbidly obese patients because anatomic landmarks are often obscured. METHODS: We evaluated the efficacy and safety of ultrasound-guided central venous cannulation in 55 patients undergoing bariatric surgery. The usefulness of ultrasonic examination combined with intraatrial electrocardiogram as a diagnostic tool for catheter misplacement was studied. RESULTS: Preliminary ultrasound examination of the neck vessels demonstrated anatomical variations in the position of internal jugular vein in 19 cases and four unrecognized asymptomatic thromboses of the right internal jugular vein. Central venous catheterization was successful in all 55 patients, in 51 with single skin puncture, and in 42 with single vein puncture. In three cases in whom the catheter was misplaced, this was detected by bedside ultrasonic examination during the procedure and immediately corrected by real-time echographic visualization. No arterial puncture, no hematoma, and no pneumothorax occurred in any patient. Successful catheter placement was also confirmed in all patients by post-operative chest X-ray. No evidence of infection or thrombosis subsequently was noted. CONCLUSIONS: The use of ultrasound guidance may increase the success rate and decrease the incidence of complications associated with central venous cannulation. The advantages of this approach is visualization of the anatomical structures at puncture site prior to skin puncture and the ability to track needle and guide-wire placement during the procedure. With its high accuracy in detecting catheter misplacement, bedside ultrasonic examination combined with intraatrial electrocardiogram may further decrease morbidity associated with misplaced central venous catheters.

Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients.

PURPOSE: The aim of the study was to compare the efficacy of parecoxib for postoperative analgesia after endoscopic turbinate and sinus surgery with the prodrug of acetaminophen, proparacetamol. MATERIALS AND METHODS: Fifty American Society of Anesthesiology (ASA) physical status I-II patients, receiving functional endoscopic sinus surgery (FESS) and endoscopic turbinectomy, were investigated in a prospective, randomized, double-blind manner. After local infiltration with 1% mepivacaine, patients were randomly allocated to receive intravenous (i.v.) administration of either 40 mg of parecoxib (n=25) or 2 g of proparacetamol (n=25) 15 min before discontinuation of total i.v. anaesthesia with propofol and remifentanil. A blinded observer recorded the incidence and severity of pain at admission to the post anaesthesia care unit (PACU) at 10, 20, and 30 min after PACU admission, and every 1 h thereafter for the first 6 postoperative h. RESULTS: The area under the curve of VAS (AUC(VAS)) calculated during the study period was 669 (28-1901) cm x min in the proparacetamol group and 635 (26-1413) cm x min in the parecoxib group (p=0.34). Rescue morphine analgesia was required by 14 patients (56%) in the proparacetamol group and 12 patients (48%) in the parecoxib (p >or= 0.05), while mean morphine consumption was 5-3.5mg and 5-2.0 mg in the proparacetamol groups and parecoxib, respectively (p >or= 0.05). No differences in the incidence of side effects were recorded between the 2 groups. Patient satisfaction was similarly high in both groups, and all patients were uneventfully discharged 24 h after surgery. CONCLUSION: In patients undergoing endoscopic nasal surgery, prior infiltration with local anaesthetics, parecoxib administered before discontinuing general anaesthetic, is not superior to proparacetamol in treating early postoperative pain.

Highlights in postoperative pain treatment.

Acute pain is a symptom that originates from actual ongoing or impending tissue damage. Pain is an individual subjective experience and varies markedly among individuals. For this reason, patient involvement is essential, with the most reliable indicator of severity being patient self-report. The main objective of postoperative pain management is the achievement of fast rehabilitation, recovery of all normal functions and reduction of postoperative morbidity. Sufficient evidence supports the hypothesis that effective analgesia modifies many of the adverse sequelae that accompany acute pain and assists in recovery. Nevertheless, despite the availability of drugs and techniques for its effective management, postoperative pain remains undertreated. It is now accepted that the solution to the problem of inadequate pain relief lies not only in the development of new analgesic drugs or technologies but also in the development of an appropriate organization to utilize existing expertise. Methods used to control postoperative pain are numerous; this review focuses on pharmacological and anesthetic methods.

Highlights in muscle relaxants.

The aim of this article is to provide an overview on neuromuscular blocking agents and a rational selection of the most appropriate agents, along with pharmacological and pharmacoeconomic considerations on neuromuscular blockers and their antagonists. Neuromuscular blocking agents are used during anesthesia to facilitate endotracheal intubation and provide surgically required paralysis. There is continuing development in the field of neuromuscular blocking agents, with new products appearing at regular intervals. All new agents come at increased costs. The proportion of anesthesia-related drug costs on a per-patient basis are small and vary from country to country, but account for no more than 12% of hospital drug budgets. However, given the large number of anesthetics performed over time, the total cost is significant. Moreover, such costs should be put into the perspective of the operating theater and patient admission costs. Appropriate selection of neuromuscular blocking agents can help not only to reduce biological costs secondary to complications, but also to make operating lists proceed smoothly and without incident. The paucity of outcome studies in relation to anesthetic drugs is not surprising given that anesthesia is used to facilitate the provision of therapy rather than being therapeutic in its own right. Accordingly, the assessment of anesthetic drugs has a different priority to therapeutic drugs. As anesthetic drugs are nontherapeutic, it is also difficult to determine the best choice of agent. However, new neuromuscular blocking agents are marketed on the basis of improvements in the frequency of side effects, safety, reliability, duration, reversibility and undesirable hemodynamic effects.

Anesthetic management of morbidly obese and super-morbidly obese patients undergoing bariatric operations: hospital course and outcomes.

BACKGROUND: Although the implications for the anesthetic and perioperative care of severely obese patients undergoing weight loss operations are considerable, current anesthetic management of super-obese (SO) patients (BMI > or =50 kg/m(2)), including super-super-obese (BMI > or =60) derives from experience with morbidly obese (MO) patients (BMI 40-49.9 kg/m(2)). We compared anesthetic and perioperative data of SO patients and MO patients undergoing weight loss operations to evaluate if anesthetic management influenced outcome. METHODS: A retrospective analysis was performed on data from 150 consecutive patients (119 MO, 31 SO) undergoing bariatric surgery between May 2000 and March 2005. Data analyzed included preoperative anesthetic assessment, anesthetic management, postoperative care, and intra- or postoperative complications. RESULTS: There were no differences in anesthetic management or in postoperative course or outcome between MO and SO patients. Intraoperative surgical complications occurred in 26% (n=8) in the SO group and 14% (n=15) in the MO group (P<0.01). CONCLUSIONS: No differences in outcome occurred between MO and SO patients undergoing bariatric operations under similar anesthetic management. Anesthesia for weight loss surgery can be safely performed on SO patients with the understanding that these patients are not at risk per se due to their higher BMI. The degree of obesity influenced only the incidence of intraoperative surgical complications.