Audrey A.A. Fiddelers

Prevalence and predictors of chronic pain after labor and delivery.

Purpose of review Labor pain is a complex phenomenon with sensory, emotional, and perceptive components and can be regarded as one of the most serious kinds of pain. Different strategies to approach acute labor pain have been developed. Chronic pain after labor and delivery has not been studied so extensively. In this review recent findings about chronic pain after labor and delivery will be discussed. Recent findings Prevalence rates of chronic pain after cesarean section are between 6 and 18% and after vaginal delivery they are between 4 and 10%. Predictors for chronic pain after cesarean section and delivery are previous chronic pain, general anesthesia and higher postdelivery pain. As labor pain is rated as one of the most serious kinds of acute pain one could make a prediction about chronic pain after labor and delivery. We speculate that effective treatment of this pain with epidural analgesia could prevent the development of chronic pain. Summary Treatment of acute pain during labor and delivery is necessary to prevent chronic pain. Future studies should focus on the long-term effects of different analgesic regimens on the development of chronic pain after labor and delivery.

Validation of the surgical fear questionnaire in adult patients waiting for elective surgery

Objectives Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. Methods Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. Results EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1–4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5–10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbachs alpha) was between 0.765–0.920 (SFQ-total), 0.766–0.877 (SFQ-s), and 0.628–0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. Discussion The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.

A review of the clinical pharmacokinetics of opioids, benzodiazepines, and antimigraine drugs delivered intranasally

BACKGROUND Interest in the development of drug-delivery devices that might improve treatment compliance is growing. A dosage formulation that is easy to use, such as intranasal application with transmucosal absorption, may offer advantages compared with other routes of drug delivery. The literature concerning intranasal application is diffuse, with a large number of published studies on this topic. Some cerebroactive pharmaceuticals delivered intranasally might follow the pathway from the nose to the systemic circulation to the brain. To determine the suitability of these drugs for intranasal drug delivery, a systematic review was performed. OBJECTIVE The aim of this review was to compare the pharmacokinetic properties of intranasal, intravenous, and oral formulations in 3 classes of cerebroactive drugs that might be suitable for intranasal delivery-opioids, benzodiazepines, and antimigraine agents. METHODS A search of MEDLINE, PubMed, Cumulative Index of Nursing and Allied Health Literature, EMBASE, and Cochrane Database of Systematic Reviews (dates: 1964-April 2009) was conducted for pharmacokinetic studies of drugs that might be suitable for intranasal delivery. A comparison of pharmacokinetic data was made between these 3 routes of administration. RESULTS A total of 45 studies were included in this review. Most of the opioids formulated as an intranasal spray reached a T(max) within 25 minutes. The bioavailability of intranasal opioids was high; in general, >50% compared with opioids administered intravenously. Intranasal benzodiazepines had an overall T(max) that varied from 10 to 25 minutes, and bioavailability was between 38% and 98%. T(max) for most intranasal antimigraine drugs varied from 25 to 90 minutes. Intranasal bioavailability varied from 5% to 40%. CONCLUSIONS This review found that intranasal administration of all 3 classes of drugs was suitable for indications of rapid delivery, and that the pharmacokinetic properties differed between the intranasal, oral, and intravenous formulations (intravenous > intranasal > oral).

Prevalence and Predictive Factors of Chronic Postsurgical Pain and Poor Global Recovery 1 Year After Outpatient Surgery.

Objectives:To prospectively describe the prevalence and predictive factors of chronic postsurgical pain (CPSP) and poor global recovery in a large outpatient population at a university hospital, 1 year after outpatient surgery. Materials and Methods:A prospective longitudinal cohort study was performed. During 18 months, patients presenting for preoperative assessment were invited to participate. Outcome parameters were measured by using questionnaires at 3 timepoints: 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale was considered to indicate moderate to severe pain. A score of ⩽80% on the Global Surgical Recovery Index was defined as poor global recovery. Results:A total of 908 patients were included. The prevalence of moderate to severe preoperative pain was 37.7%, acute postsurgical pain 26.7%, and CPSP 15.3%. Risk factors for the development of CPSP were surgical specialty, preoperative pain, preoperative analgesic use, acute postoperative pain, surgical fear, lack of optimism, and poor preoperative quality of life. The prevalence of poor global recovery was 22.3%. Risk factors for poor global recovery were recurrent surgery because of the same pathology, preoperative pain, preoperative analgesic use, surgical fear, lack of optimism, poor preoperative and acute postoperative quality of life, and follow-up surgery during the first postoperative year. Discussion:Moderate to severe CPSP after outpatient surgery is common, and should not be underestimated. Patients at risk for developing CPSP can be identified during the preoperative phase.

Pharmacokinetics, Analgesic Effect, and Tolerability of a Single Preprocedural Dose of Intranasal Fentanyl in Patients Undergoing Drain Removal After Breast Reduction or Augmentation Surgery: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

BACKGROUND Although acetaminophen is used to reduce pain after breast reduction or augmentation surgery, pain during the removal of the surgical drains is typically not specifically treated. Intranasally administered fentanyl may be suitable for pain control during removal of drains. The reported therapeutic window of fentanyl is between 0.2 and 1.2 ng/mL. OBJECTIVE The aim of this study was to evaluate the analgesic effect, tolerability, and pharmacokinetics of a single preprocedural dose of intranasal fentanyl administered before removal of surgical drains in patients who had undergone breast reduction or augmentation surgery. METHODS This was a randomized, double-blind, prospective study in healthy women (American Society of Anesthesiologists physical status I or II) between the ages of 18 and 65 years who were scheduled to undergo removal of surgical drains 1 to 4 days after breast reduction or augmentation surgery. A single dose of fentanyl nasal spray 0.05 mg/0.1 mL or placebo (preserved normal saline) 0.1 mL was administered 10 minutes before removal of drains. Because drain removal is generally carried out without specific analgesia, no rescue medication was provided. Pain intensity was measured on a visual analog scale (VAS) from 0 = no pain at all to 100 = worst pain possible. Pain intensity was evaluated immediately before administration of study medication (t = 0), at the time of drain removal (t = 10), and at 15, 20, 25, 40, and 70 minutes after administration of study medication. Safety measures included oxygen saturation, respiratory rate, heart rate, and blood pressure. Local and systemic adverse events were elicited by direct questioning throughout the study. Blood samples for pharmacokinetic analysis were collected at baseline and at 5, 10, 15, 30, 60, and 120 minutes after administration of study medication. The population pharmacokinetic parameters of fentanyl were calculated according to a 1-compartment open model with an iterative 2-stage Bayesian fitting procedure. RESULTS Thirty-six women were randomized to treatment, and 33 completed the study. Their mean (SD) age was 39.2 (13.0) years, and their mean weight was 68.9 (10.7) kg. Mean VAS scores at baseline were 14.8 (17.8) for the fentanyl group and 6.0 (9.7) for the placebo group (P = NS); at the time of drain removal, the corresponding VAS scores were 31.0 (20.6) and 33.8 (25.7) (P = NS). Analysis of a random-effects model with mean VAS scores as a function of time as the dependent variable indicated a significant difference in mean VAS scores between the fentanyl and placebo groups (P = 0.006). The overall incidence of adverse events was 39.4% (13/33). Among the 17 patients in the fentanyl group, 8 reported > or =1 adverse event; among the 16 patients in the placebo group, 9 reported > or =1 adverse event. A mean estimated C(max) of 0.184 (0.069) ng/mL was reached at 13.76 (3.56) minutes after administration of intranasal fentanyl. The mean measured C(max) was 0.22 (0.088) ng/mL. CONCLUSIONS In these women who had undergone breast reduction or augmentation surgery, a single preprocedural dose of intranasal fentanyl was significantly more effective than placebo in reducing pain intensity over the hour after removal of surgical drains. However, there was no significant difference in pain intensity between fentanyl at the time of drain removal and placebo. Intranasal fentanyl was generally well tolerated. At the dose used (0.05 mg), plasma fentanyl concentrations were below the reported therapeutic window.

Pharmacokinetics and Tolerability of Nasal Versus Intravenous Midazolam in Healthy Dutch Volunteers: A Single-Dose, Randomized-Sequence, Open-Label, 2-Period Crossover Pilot Study

BACKGROUND Intranasal (IN) midazolam is a potential alternative to rectal diazepam for the acute treatment of epileptic seizures. OBJECTIVE The purpose of this pilot study was to investigate the pharmacokinetics and tolerability of IN midazolam (50 mg/mL) compared with intravenous (IV) midazolam (2.5 mg) in healthy adult volunteers. METHODS In this single-dose, randomized-sequence, open-label, 2-period crossover pilot study subjects were randomly assigned to receive IN or IV midazolam, with a washout period of at least 5 days between treatments. The 50-mg/mL IN midazolam formulation consisted of 5 mg midazolam base per 0.1 mL (1 spray) and was administered once in 1 nostril. The IV midazolam solution (2.5 mg) was infused over 10 seconds. Blood samples were taken before and at regular intervals up to 240 minutes after dosing. Pharmacokinetic data (ie, C(max), T(max), t(½), and AUC) were analyzed using a 2-compartment model. RESULTS Of 9 volunteers screened and enrolled, 7 completed the study (mean age 34.1 [9.0] years; mean weight, 68.6 [10.4] kg, range 53-89 kg; 6 men, 3 women; all white). The mean C(max) of 78 (40) ng/mL was reached 44 minutes after IN administration, whereas the mean C(max) was 51 (5) ng/mL after IV administration. The mean estimated C(t=5 min) was 31.4 (28.1) ng/mL after IN administration. The elimination t(½) was 1.9 (0.41) hours for IN midazolam and 2.3 (0.19) hours for IV midazolam. The bioavailability of IN midazolam was 82%. There were few adverse events, with a local burning feeling in the nose being the most reported event (6 of 7 subjects). CONCLUSIONS In this select group of healthy volunteers, concentrations of midazolam >30 ng/mL were reached within 5 minutes of IN administration at a dose of 5 mg/0.1 mL. A burning feeling in the nostril was the main adverse effect. Additional research is needed to evaluate the safety profile, convenience, satisfaction, and efficacy of nasal midazolam in the treatment of adults with seizures. This trial is registered at www.isrctn.org, No. ISRCTN79059168.

Prevalence and Predictors of Quality of Recovery at Home After Day Surgery

AbstractTraditionally, major complications and unanticipated admission/readmission rates were used to assess outcome after day surgery. However, in view of the relative absence of major complications the quality of recovery (QOR) should be considered one of the principal endpoints after day surgery. In our study, the level of QOR is defined by a combination of the Global Surgical Recovery (GSR) Index and the Quality of Life (QOL).The aim of this study was to analyze prevalence and predictors of QOR after day surgery on the fourth postoperative day.Elective patients scheduled for day surgery from November 2008 to April 2010 were enrolled in a prospective cohort study. Outcome parameters were measured by using questionnaire packages at 2 time points: 1 week preoperatively and 4 days postoperatively. Primary outcome parameter is the QOR and is defined as good if the GSR index >80% as well as the postoperative QOL is unchanged or improved as compared with baseline. QOR is defined as poor if both the GSR index ⩽80% and if the postoperative QOL is decreased as compared with baseline. QOR is defined as intermediate in all other cases. Three logistic regression analyses were performed to determine predictors for poor QOR after day surgery.A total of 1118 patients were included. A good QOR was noted in 17.3% of patients, an intermediate QOR in 34.8%, and a poor QOR in 47.8% 4 days after day surgery. The best predictor for poor QOR after day surgery was type of surgery. Other predictors were younger age, work status, and longer duration of surgery. A history of previous surgery, expected pain (by the patient) and high long-term surgical fear were significant predictors of poor QOR in only 1 of 3 prediction models.The QOR at home 4 days after day surgery was poor in the majority of patients and showed a significant procedure-specific variation. Patients at risk for poor QOR can be identified during the preoperative period based on type of surgery, age, work status, and the duration of the surgery.

Prevalence and Predictive Factors of Chronic Postsurgical Pain and Global Surgical Recovery 1 Year After Outpatient Knee Arthroscopy: A Prospective Cohort Study

AbstractOutpatient knee arthroscopy is one of the most commonly performed surgical procedures. Previous research has demonstrated that chronic postsurgical pain (CPSP) after outpatient surgery is prevalent. Our objective was to determine the prevalence and predictive factors of CPSP and Global Surgical Recovery (GSR) 1 year after knee arthroscopy.A prospective longitudinal cohort study was performed. Patients were included during an 18-month period. Data were collected by using 3 questionnaires: at 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale (NRS) was defined as moderate to severe pain. A score of ⩽80% on the Global Surgical Recovery Index was defined as poor GSR. Stepwise logistic regression analysis was performed to determine which variables were predictors for CPSP and poor GSR.The prevalence of moderate to severe preoperative pain in patients undergoing knee arthroscopy (n = 104) was 71.2%, of acute postsurgical pain 37.5%, and of CPSP 32.7%. Risk factors for CPSP were the presence of preoperative pain and preoperative analgesic use, with odds ratios of 6.31 (1.25–31.74) and 4.36 (1.58–12.07), respectively. The prevalence of poor GSR 1 year after outpatient knee arthrosocpy was 50.0%. Poor GSR 4 days after the surgery was a risk factor with an odds ratio of 8.38 (0.92–76.58) and quality of life 4 days after surgery was a protective factor with and odds ratio of 0.10 (0.02–0.64).Both CPSP and poor GSR are common 1 year after knee arthroscopy. Patients at risk for CPSP can be identified during the preoperative phase. Prediction of poor GSR 1 year after surgery is mainly related to early postoperative recovery.

Controlled-Release Oxycodone Versus Naproxen at Home After Ambulatory Surgery: A Randomized Controlled Trial

Background Strong opioids in the home setting after ambulatory surgery have rarely been studied for fear of hazardous adverse effects such as respiratory depression. Objectives We compared the efficacy of paracetamol/controlled-release (CR) oxycodone and paracetamol/naproxen for treatment of acute postoperative pain at home after ambulatory surgery. Secondary outcomes were adverse effects of study medication, treatment satisfaction, and postoperative analgesic compliance. Methods Patients undergoing ambulatory knee arthroscopy or inguinal hernia repair surgery (n = 105) were randomized into 3 groups: Group1 paracetamol/naproxen (n = 35), Group 2 paracetamol/CR oxycodone for 24 hours (n = 35), and Group 3 paracetamol/CR oxycodone for 48 hours (n = 35). Pain intensity at movement and at rest using a visual analog scale as well as satisfaction with postoperative analgesia and side effects were recorded for up to 48 hours postoperatively. Compliance with study medication was also assessed. Results For pain at movement and at rest, no significant differences were found between the paracetamol/naproxen group and either the paracetamol/CR oxycodone for 24 hours group (β = 2.6 [4.9]; P = 0.597) or the paracetamol/CR oxycodone for 48 hours (β = –1.7 [5.1]; P = 0.736). No major adverse effects of study medication were registered and satisfaction with postoperative pain treatment was high in all groups. Compliance was comparable across the groups. Despite clear instructions, 8 patients with the lowest pain scores did not use any of the prescribed pain medication. Conclusions Paracetamol/CR oxycodone and paracetamol/naproxen are equally effective in treatment of acute postoperative pain at home after ambulatory surgery with comparable patient satisfaction level. We suggest paracetamol/CR oxycodone to be a valuable alternative for the current paracetamol/naproxen gold standard, particularly in patients with a contraindication for nonsteroidal anti-inflammatory drugs. ClinicalTrials.gov identifier: NCT02152592.

Prevalence and Predictors of Patient Nonadherence to Pharmacological Acute Pain Therapy at Home After Day Surgery: A Prospective Cohort Study

Good adherence to prescribed analgesics can be crucial to suppress or even prevent acute postoperative pain after day surgery. The aim of this study was to analyze prevalence and predictors of analgesic nonadherence after day surgery.