Processes of change in Acceptance and Commitment Therapy and Applied Relaxation for long-standing pain.

BACKGROUND: The utility of cognitive behavioural (CB) interventions for chronic pain has been supported in numerous studies. This includes Acceptance and Commitment Therapy (ACT), which has gained increased empirical support. Previous research suggests that improvements in pain catastrophizing and psychological inflexibility are related to improvements in treatment outcome in this type of treatment. Although a few studies have evaluated processes of change in CB-interventions, there is a particular need for mediation analyses that use multiple assessments to model change in mediators and outcome over time, and that incorporate the specified timeline between mediator and outcome in the data analytic model. METHODS: This study used session-to-session assessments to evaluate if psychological inflexibility, catastrophizing, and pain intensity mediated the effects of treatment on pain interference. Analyses were based on data from a previously conducted randomized controlled trial (n = 60) evaluating the efficacy of ACT and Applied Relaxation (AR). A moderated mediation model based on linear mixed models was used to analyse the data. RESULTS: Neither catastrophizing nor pain intensity mediated changes in pain interference for any of the treatments. In contrast, psychological inflexibility mediated effects on outcome in ACT but not in AR. CONCLUSIONS: Results add to previous findings illustrating the role of psychological inflexibility as a mediator in ACT.

Acceptance and commitment therapy for fibromyalgia: a randomized controlled trial.

BACKGROUND: Fibromyalgia (FM) is characterized by widespread pain and co-morbid symptoms such as fatigue and depression. For FM, medical treatments alone appear insufficient. Recent meta-analyses point to the utility of cognitive behaviour therapy (CBT), but effects are moderate. Within the continuous development of CBT, the empirical support for acceptance and commitment therapy (ACT) has increased rapidly. ACT focuses on improving functioning by increasing the patient's ability to act in accordance with personal values also in the presence of pain and distress (i.e., psychological flexibility). However, no study has yet explored the utility of ACT in FM. OBJECTIVES: To evaluate the efficacy of ACT for FM and the role of psychological inflexibility as a mediator of improvement. METHODS: In this randomized controlled trial, ACT was evaluated in comparison to a waiting list control condition. Forty women diagnosed with FM participated in the study. Assessments were made pre- and post-treatment and at 3 months of follow-up. The ACT intervention consisted of 12 weekly group sessions. RESULTS: Significant differences in favour of ACT were seen in pain-related functioning, FM impact, mental health-related quality of life, self-efficacy, depression, anxiety and psychological inflexibility. Changes in psychological inflexibility during the course of treatment were found to mediate pre- to follow-up improvements in outcome variables. CONCLUSIONS: The results correspond with previous studies on ACT for chronic pain and suggest the utility of ACT for FM as well as the role of psychological inflexibility as a mediator of improvement.

Pharmacokinetics after an intravenous single dose of the opioid ketobemidone in children.

BACKGROUND: Ketobemidone is often used as an alternative to morphine in children in the Scandinavian countries. The aim of this clinical trial was to explore the pharmacokinetics of ketobemidone in children because these properties have not been reported previously. METHODS: Thirty children, newborn to 10 years, scheduled for elective surgery were included in the trial. Ketobemidone hydrochloride was administered as a single intravenous bolus dose and ketobemidone and norketobemidone concentrations were measured by LC-MS over 8 h. Pharmacokinetic parameters were determined using compartmental methods. RESULTS: Six children were excluded from pharmacokinetic analysis because of incomplete blood sampling. The values of ketobemidone clearance (l/h/kg) given as median (range) were 0.84 (0.29-3.0) in Group A (0-90 days), 0.89 (0.55-1.35) in Group B (1-2.5 years) and 0.74 (0.50-0.99) in Group C (7-10 years). The corresponding values for apparent volume of distribution (l/kg) were 4.4 (3.7-6.9) (Group A), 2.6 (2.0-5.6) (Group B) and 3.9 (2.7-5.0 (Group C), and for elimination half-life (h) 3.0 (1.4-8.9) (Group A), 2.0 (1.2-4.7) (Group B) and 3.7 (2.4-6.9) (Group C), respectively. In the two neonates the elimination half-life was almost 9 h. The metabolite norketobemidone did not reach levels above the limit of quantification (0.07 ng/ml) in any of the patients. CONCLUSION: The pharmacokinetic parameters of ketobemidone in children older than 1 month appear to be similar to those in adults. Because of the large interindividual variability of the pharmacokinetics in neonates, further studies especially in this age group are warranted.

Comparison of the analgesic efficacy of ketobemidone and morphine for management of postoperative pain in children: a randomized, controlled study.

BACKGROUND: Ketobemidone has been used as an analgesic for postoperative pain in children, but to our knowledge the effect and occurrence of adverse effects of ketobemidone compared to morphine is not known. The aim was to determine if the analgesic potency and the occurrence of adverse effects of ketobemidone differ from morphine when administered to children, as measured by patient-controlled analgesia consumption (PCA) for postoperative pain. METHODS: Sixty healthy children, aged 6 to 16 years, scheduled for elective surgery were randomized to receive either ketobemidone (Ke) 1 mg ml(-1) or morphine (Mo) 1 mg ml(-1) for postoperative pain through PCA. Drug consumption (microg kg(-1) h(-1)), the number of PCA doses, pain intensity, and adverse effects were recorded at regular intervals. RESULTS: Data on total drug consumption were based on 26 children in the Ke group and 28 in the Mo group. A non-statistically significant difference for total mean consumption of ketobemidone (18.6 microg kg(-1)h(-1)) and morphine (23.2 microg kg(-1)h(-1)) was obtained. The mean dose ratio (Mo/Ke) was 0.80 and the median was 0.94. Children's characteristics, loading dose, PCA doses, VAS scores, and adverse effects showed no significant differences between the groups. CONCLUSION: The analgesic potency and adverse effects of ketobemidone are similar to morphine when used for postoperative pain management in children.

Retrospective evaluation of continuous epidural infusion for postoperative pain in children.

BACKGROUND: The safety and efficacy of postoperative epidural analgesia (EDA) in children are not well documented in larger series of patients given routine postoperative care. The aims of this study were to evaluate the efficacy of pain relief, determine the incidence and type of complications during the entire period of epidural pain treatment in children, and assess the factors affecting efficacy METHODS: Children treated postoperatively with an EDA infusion during the period 18 September 1994 to 1 January 1999 were studied. Data regarding the age, gender, efficacy of analgesia, duration of epidural infusion, types of side-effects and complications, reasons for discontinuation, and types and duration of surgery were collected daily by the Acute Pain Treatment Service. The sensory dermatomal level of the surgical incision site was included retrospectively. RESULTS: Five hundred and eighteen epidural infusions were given to 476 children. Pain relief was rated as 'good' at 76% of visits. There were no major complications or sequelae. Thirty-seven per cent of the epidural infusions were prematurely discontinued, and 21% were discontinued because of unsatisfactory analgesia. Factors related to a higher percentage of unsatisfactory function were surgical incision site located above the umbilicus, gastroenterologic surgery, protracted surgery and age. Age and duration of surgery were significantly related to unsatisfactory function. CONCLUSION: This study shows that continuous epidural infusion for postoperative pain was satisfactory in most cases, and that no major side-effects or complications occurred in children nursed on regular wards. The early recognition of unsatisfactory function of an EDA is important for a child's well being.

Ropivacaine pharmacokinetics after caudal block in 1-8 year old children.

We studied the pharmacokinetics after caudal block of ropivacaine (2 mg ml-1, 1 ml kg-1) performed in 20 children aged 1-8 yr undergoing subumbilical surgery, in this open, non-comparative, multicentre study. Venous blood samples were collected up to 12-36 h. The mean (SD) peak plasma concentration, 0.47 (0.16) mg litre-1, was achieved after 12-249 min. The free fraction was 5% and the highest individual peak plasma concentration of free ropivacaine was 0.04 mg litre-1. Clearance was 7.4 (1.9) ml min-1 kg-1 and the terminal half-life 3.2 (0.8) h. Thus, the free plasma concentrations of ropivacaine were well below those associated with toxic symptoms in adults and the capacity to eliminate ropivacaine seems to be well developed in this age group. In this open study of 20 patients, ropivacaine was well tolerated and provided satisfactory postoperative pain relief without observable motor block.

Preoperative psychological preparation for children undergoing ENT operations: a comparison of two methods.

A psychological preparation programme was developed for outpatient surgery in children. The purpose of this study was to determine if the programme could increase retrieval of information and reduce anxiety prior to ENT surgery. After ethical committee approval, 160 children and their parents were included. Eighty children (group 1) received conventional verbal information from an ENT nurse, and another 80 children (group 2) received specific information, including role-play, from a nurse anaesthetist at a preadmission visit. Children's and parents' experience of premedication, operation theatre (OR), i.v.-needle insertion and induction of anaesthesia were evaluated from a self-rating questionnaire. The questionnaire included ratings for anxiety and satisfaction with information and care. The results indicate a clear improvement of the preoperative acquisition of knowledge in all age groups. When it comes to alleviation of fear, a positive effect of the preparation programme was noticed, especially among the younger children (< 5 years), while preoperative anxiety overall was a significantly smaller problem among the older children. The effects of the programme were also related to previous experience of anaesthesia and most beneficial among young children with such experience. Overall, the most negative procedure reported by the children was the i.m. injection for premedication (a routine which was abandoned as a result of the study), followed by the insertion of the i.v. -needle. The parents experienced watching their child fall asleep during induction of anaesthesia as most negative, followed by the insertion of the i.v.-needle. Parents also reported more satisfaction and less anxiety after having received specific information and preparation preoperatively. It was concluded that this preoperative preparation programme is useful in all age groups with regard to information, while alleviation of anxiety and fear was seen mainly among the younger children with previous experience of anaesthesia.

Alleviation of the pain of venepuncture in neonates.

UNLABELLED: A recent study has shown venepuncture to be more effective and less painful than heel-lancing when a single blood test is performed in neonates [Larsson, Pediatrics (in press)]. The aim of the present study was to investigate the value of EMLA applied on the dorsum of the hand when sampling blood in neonates. METHODS: This was a controlled randomized and double-blinded study. One hundred and twenty neonates were randomly allocated to two groups, EMLA or placebo. Five hundred milligrams (0.5 ml) of EMLA or placebo was placed on the dorsum of the hand, covered with an occlusive dressing, and left in place for 60 minutes. For venepuncture, a needle measuring 0.9 x 40 mm was used. The two groups were also compared as regards the total time needed to complete the PKU test and the number of skin punctures required. The facial reaction was videotaped and later analysed by two blinded observers using the Neonatal Facial Coding System (NFCS). RESULTS: No side effects occurred, except for a temporary blanching or redness of the skin, which disappeared within minutes. Nociceptive response: After skin puncture, the NFCS scores were significantly lower in the EMLA group than in the placebo group (median 287 and 374, respectively). After the first skin puncture, a cry was recorded in 35/55 cases (64%) in the EMLA group and in 38/56 cases (68%) in the placebo group, this difference was not significant. The duration of the first cry was significantly shorter in the EMLA than in the placebo group (median 12 and 31 s, respectively). CONCLUSION: In comparison with a placebo, EMLA significantly reduces the pain caused by venepuncture on the dorsum of the hand and does not complicate puncture of the vein.

Venipuncture is more effective and less painful than heel lancing for blood tests in neonates.

OBJECTIVE: Heel lancing has hitherto been the method of choice for screening tests of inborn errors of metabolism in neonates. Eutectic mixture of local anesthetic has little, if any, analgesic effect when applied to the heel of pre- and full-term infants. Today there seems to be no practical method that effectively alleviates the pain caused by heel lancing. The aim of this study was to investigate whether other methods, such as venipuncture of the dorsal side of the hand, are less painful and more efficient than heel lancing in neonates. METHODS: One hundred twenty healthy, full-term infants who underwent testing for phenylketonuria (PKU) were included in the study. They were randomized into three groups: a venipuncture group (VP) (n = 50), a heel-lance group with a small lancet (SL) (n = 50), or a large lancet (LL) (n = 20). Pain reactions were assessed by the Neonatal Facial Coding System (NFCS). The latency and duration of the first cry as well as the total screaming time was analyzed. The efficacy of the method was assessed by the time taken to complete the PKU test and number of times the skin had to be punctured. RESULTS: Nociceptive response. The NFCS scores after the first skin puncture were: VP, 247; SL, 333; and LL, 460. The NFCS scores were significantly lower in the VP than in the groups subjected to heel lancing. During the first 60 seconds after skin puncture, 44% of the infants cried in the VP group, compared with 72% and 85% in the SL and LL groups, respectively. Efficacy. A successful PKU test with only one skin puncture was performed in 86% of the VP group, but in only 19% in the SL group and 40% in the LL group. The total time needed to obtain the PKU blood sample was 191 seconds (median) in the VP group, 419 seconds in the SL group, and 279 seconds in the LL group. CONCLUSION: Venipuncture is more effective and less painful than heel lancing for blood tests in neonates.

Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital wards: prospective experience with 1,030 surgical patients.

BACKGROUND: The efficacy and safety of patient-controlled epidural analgesia (PCEA) for postoperative analgesia on hospital wards was studied. METHODS: Postoperative analgesia was provided for 1,030 patients with PCEA using 0.05% bupivacaine and fentanyl, 4 microg/ml, in a standardized manner. Patients were seen at least twice a day by the staff of the anesthesia pain management service. Prospectively gathered data included verbal pain scores at rest and activity (0-10); consumption of bupivacaine and fentanyl; and incidences of pruritus, nausea, sedation, hypotension, motor block, and respiratory depression. Descriptive statistics were used. Risk factors for side effects were determined using logistic regression. RESULTS: The study included 552 women and 477 men who underwent a median (mode) of 3 (2) days of PCEA. Their mean age was 59 +/- 16 yr and their mean weight was 76 +/- 19 kg. There were 454 abdominal, 165 gynecologic, 126 urologic, 108 vascular, 90 thoracic, 83 orthopedic, and 4 plastic surgical procedures. Median (mode) pain scores were 1 (0) at rest and 4 (5) with activity on postoperative day 1. Incidences of side effects were 16.7% (pruritus), 14.8% (nausea), 13.2% (sedation), 6.8% (hypotension), 2% (motor block), and 0.3% (respiratory depression). Reasons for termination of PCEA were elective (82%), displaced epidural catheter (12%), anticoagulation (3%), infection (1%), side effects (1%), inadequate analgesia (1%), and other (<1%). Risk factors for side effects were female sex, patient weight <73 kg, patient age <58 yr, bupivacaine and fentanyl consumption >9 ml/h, use of analgesic adjuncts, and lumbar placement of epidural catheters. CONCLUSION: Patient-controlled epidural analgesia provides effective and safe postoperative analgesia on hospital wards.

Plasma concentrations of bupivacaine in neonates after continuous epidural infusion.

This study reports plasma bupivacaine concentrations in 13 neonates who received lumbar epidural anesthesia during major abdominal surgery. A bolus of 1.8 mg/kg of bupivacaine (2.5 mg/mL) was administered after induction of anesthesia, followed by a continuous infusion of 0.2 mg.kg-1.h-1 (1.25 mg/mL). Plasma concentrations of total and free bupivacaine and alpha 1-acid-glycoprotein (AAG) were determined. Results are presented as mean (+/-SEM). At 48 h, five of nine patients still had increasing total plasma concentrations, and the total bupivacaine concentrations ranged between 0.7 and 3.1 micrograms/mL. The plasma levels of AAG increased significantly between 1 and 24 h (4.3 +/- 2.3 nM and 7.7 +/- 2.3 nM, respectively) (P = 0.018). The free concentrations of bupivacaine were relatively unchanged at 1 and 24 h (84 +/- 20 ng/mL and 58 +/- 15 ng/mL, respectively). No adverse events occurred during the study period. In conclusion, the dose administered in this study appears to be safe. However, a substantial number of patients still had increasing concentrations of total plasma bupivacaine at 48 h. Furthermore, the interindividual variation was considerable. These observations cause concern about the safety of epidural infusions longer than 48 h in the age group studied.

[The routine sampling procedure for PKU should be changed. Venous puncture is less painful than heel lancing]. / Praxis vid PKU-provtagning bör ändras. Venpunktion gör mindre ont än hälstick.

All newborns in Sweden are screened for phenylketonuria (PKU), among other things, blood usually being sampled by heel lancing. Because it is unnecessarily painful, however, this form of sampling in newborns has recently been questioned. There is reason to recommend sampling from a dorsal hand vein as the method of choice for PKU screening purposes.

Rectal administration of morphine in children. Pharmacokinetic evaluation after a single-dose.

BACKGROUND: There is limited knowledge about the pharmacokinetics of morphine and its metabolites after rectal administration in children. In this study the pharmacokinetics of two different rectal formulations of morphine were examined and compared with intravenous morphine. METHODS: Children undergoing elective surgery received rectal morphine 0.2 mg/kg before start of surgery. Ten children (mean age 14 months) received morphine rectally in a hydrogel formulation and another 10 children (mean age 16 months) received morphine rectally in a parenteral formulation. For comparison, 6 children (mean age 21 months) were given the same dose intravenously. The plasma concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by HPLC over 6 h after drug administration. RESULTS: The mean rectal bioavailability of morphine was 35% (range 18-59) after hydrogel administration and 27% (range 6-93) after the solution. Mean values of Cmax were 76 nmol/l (25-129) and 56 nmol/1 (15-140), respectively. The results showed that morphine gel had a significantly higher bioavailability (P < 0.02) than the solution. The ratios of plasma (M3G + M6G) to morphine were higher after rectal administration (mean 7.5-8.7) than after i.v. injection (mean 5.3), indicating the presence of first-pass metabolism using the rectal route. CONCLUSIONS: The rectal morphine hydrogel has pharmacokinetic properties which makes it a useful formulation for premedication and pain alleviation in paediatric patients.

Age at acquisition of Helicobacter pylori infection: comparison of a high and a low prevalence country.

Helicobacter pylori (HP) is now generally accepted as the main aetiological agent in chronic active gastritis and peptic ulcer. Infection with HP is widespread, but the routes of transmission are still unclear. Several studies have shown increasing prevalence of antibodies against HP with age. In developing countries, age at peak incidence of seroconversion is probably considerably lower than in developed countries. We performed a cross-sectional study to determine the age at maximum incidence of seroconversion to HP in a high-prevalence country (Ethiopia) and in a low-prevalence country (Sweden). Sera from 242 Ethiopian children, aged 2-14 years and from 295 Swedish children aged 1-15 years were analysed using an enzyme linked immunosorbent assay (ELISA) for detecting immunoglobulin G (IgG) antibodies. In Ethiopia, a comparison was made of a local and a reference strain for preparation of the antigen, but there was little difference in outcome. A comparison between antigen prepared from the reference strain and the pooled antigen used in the Swedish study also showed little difference. The sharpest rise in seroprevalence was found in the age range 2-4 years. Among 4-year-olds, some 60% had already seroconverted, and among 12-year-olds almost 100% had done so. In Sweden, the sharpest rise appeared between the ages of 9 and 10 years. Above 10 years of age seroprevalence was around 20%. Infection with HP is acquired in early childhood in Ethiopia, but somewhat later, although still before the teens, in Sweden. To determine properly the risk factors for infection with HP, possible exposure must be assessed around the age of seroconversion, since seropositivity may remain for a long time but environmental factors may have changed since primary infection.

Regional variations in skin perfusion and skin thickness may contribute to varying efficacy of topical, local anaesthetics in neonates.

The national Swedish screening programme for inborn errors of metabolism includes blood sampling from all neonates. Heel lancing has hitherto been the method of choice for these screening tests. Studies have recently been done to find out whether the use of EMLA can alleviate pain caused by heel lancing. EMLA had little, if any effect when applied to the heel of full term babies. Similar results were reported concerning preterm infants. Other authors have found that differences in skin thickness or in skin blood perfusion may influence the effect of EMLA. The aim of this study was to establish whether differences in skin thickness or in skin blood perfusion were present in three regions: the forehead, the dorsum of the hand and the heel. Ten healthy full term neonates were included in the study on skin perfusion. Measurements were made with a laser Doppler flux meter. Twenty-seven healthy full term neonates were included for measurements of skin thickness using a high frequency B-mode ultrasonic meter. The heel skin perfusion was two to three times higher than the skin perfusion at the dorsum of the hand and at the forehead but there was no significant difference when comparing skin thickness of the heel with the dorsum of the hand and the forehead. A rapid clearance of a topically applied local anaesthetic, due to high cutaneous blood flow, may explain why EMLA seems to be of little value when it is applied to the neonatal heel.

Procedural pain in a paediatric surgical emergency unit.

Pain induced by various types of procedures was assessed in the Paediatric Surgical Emergency Department at St Göran's Children's Hospital in Stockholm. Assessments of pain were obtained from the nurse, the parent, and children over 10 years of age by means of a visual analogue scale. In children aged 3-9 years, the Smiley Five-Face Scale was used. The nurse and the parent also answered questionnaires about analgesic medication, the child's behaviour, and the parent's overall opinion of the pain management, etc. Irrigation of the glans penis because of balanitis, treatment of fractures and paronychia were considered to be the most painful procedures. Forty-four per cent of the children cried during the procedure and 16% fought against being restrained. In 24% of the cases, the child was judged to be in a state of "panic". In conclusion, we believe that the pain induced by procedures in the emergency rooms is unacceptably high. Children estimate higher pain scores than parents and nurses do. There was a poor correlation between the parent's and child's estimates of pain. Parents are not well informed about the possibilities for pain treatment. Infants and children attending emergency rooms must also benefit from recent advances in the treatment of pain.

Does a local anaesthetic cream (EMLA) alleviate pain from heel-lancing in neonates?

EMLA cream is an effective local anaesthetic agent for venipunctures in adults and children. The aim of this double-blind, randomised, and placebo-controlled study was to evaluate the effect of EMLA when heel-lancing was performed in neonates. On their third day of life, fullterm healthy infants, who underwent testing for phenylketonuria (PKU) by heel-lancing, were consecutively included in the study. One hundred and twelve neonates were allocated to eight groups according to the application time of EMLA or placebo (10 to 120 minutes). Thus in each group seven infants received active substance and seven placebo. The response to the nociceptive stimulation was assessed by studying the occurrence of a pain cry. No analgesic effect of EMLA was found. There were no adverse effects.

Inhalational anaesthesia at the extremes of age: paediatric anaesthesia.

The relevant physiological and pharmacokinetic differences between adults and infants and children are considered, and the advantages and disadvantages of the available inhalational anaesthetics are discussed. Desflurane shows promise as a new paediatric anaesthetic as it allows rapid changes in the depth of anaesthesia. However, irritant effects on the airways make desflurane unsuitable for induction. Desflurane anaesthesia, following halothane induction, seems to be well tolerated.