A comparison of 50, 100 and 200 mg of intra-articular pethidine during knee joint surgery, a controlled study with evidence for local demethylation to norpethidine.

Pethidine (meperidine) is a compound with both local anaesthetic and opioid agonist properties. We have in a recent study demonstrated that pethidine could be an interesting alternative to prilocaine in arthroscopy with local anaesthetic technique. Therefore, we investigated, in a controlled randomized double-blind study, the effect of three doses of pethidine compared with a standard local anaesthetic, in patients subjected to arthroscopic knee joint surgery. Ten patients in each group received 50 mg (P50), 100 mg (P100), 200 mg (P200) of pethidine or prilocaine (5 mg/ml) + adrenaline (4 mg/ml) (PC), injected intra-articularly (i.a.) before surgery. We measured pain intensity and discomfort during arthroscopy and pain intensity at rest and at movement, nausea and tiredness for 3 days post-operatively at regular intervals using the VAS-technique. We also measured the concentration of pethidine and its demethylated metabolite, norpethidine, in plasma by collecting blood samples at 20, 40, 60, 80, 140 and 200 min following injection, and in synovial fluid which was collected through the arthroscope at the start and the end of the surgery. It was found that significantly more patients in the P50 group (n = 6) needed general anaesthesia due to intense pain than those in the P100 group (n = 1), P200 group (n = 0) or the PC group (n = 1). The PC group required significantly more analgesics and had a significantly higher calculated total sum of pain scores at movement post-operatively, than the other three groups. The P200 group more often reported tiredness post-operatively than the other three groups. We conclude that 100 or 200 mg pethidine i.a. produces satisfactory anaesthesia for surgery. There was a rapid transfer of pethidine from synovial fluid to plasma, resulting in plasma levels earlier reported to produce centrally mediated effects, such as analgesia and tiredness. We found much higher concentrations of norpethidine in the synovial fluid than in plasma, suggesting a local demethylation in the knee joint tissues. This site of drug oxidation has not earlier been demonstrated neither in vitro nor in vivo. The results suggest that pethidine given i.a. in the dose range of 50 to 200 mg results in analgesia due to both peripheral and central mechanisms. The significant systemic uptake of pethidine can cause unwanted side-effects.

Pharmacokinetics and clinical effect during continuous epidural infusion with ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief.

BACKGROUND: Ropivacaine has shown less systemic toxicity than bupivacaine, and comparatively low muscle-blocking properties could constitute another advantage when used epidurally for obstetric pain relief. We aimed primarily to compare maternal and foetal drug disposition following continuous epidural infusion of ropivacaine or bupivacaine. METHODS: Twenty-four full-term, nulliparous women were randomized to continuous epidural infusion (10 ml/h) of ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief in a double-blind, parallel-group design. Maternal blood samples were collected up to 24 h after the end of infusion as well as taken from the umbilical cord at the time of delivery. Sensory and motor block as well as analgesia were assessed. All the women were monitored by cardiotocography and neonatal assessment was performed. RESULTS: The sensory block was adequate for both drugs. Higher plasma levels (total and free) were seen with ropivacaine, although the infusion with bupivacaine continued on average for about 2 hours longer. However, the ratios between maternal and umbilical blood concentrations were similar for both drugs. Normal neonatal Apgar and neonatal adaptive capacity scores (NACS) were found in both groups. CONCLUSION: A continuous epidural infusion of 25 mg/h ropivacaine or bupivacaine both produced good labour pain relief. Higher total and free plasma concentrations were seen for ropivacaine. The ratios between maternal and umbilical plasma levels were similar for both drugs.

Intrathecal administration of sameridine to patients subjected to arthroscopic knee joint surgery.

BACKGROUND: Sameridine, a new substance with both local anesthetic and opioid effects, was administered intrathecally for the first time to humans, i.e. in patients subjected to arthroscopic knee joint surgery. METHOD: A dose-escalating (10, 15, 20 and 25 mg), open study was performed in 33 patients. Only two patients were included in the 25 mg group. RESULTS: Sameridine provided good quality of surgical anesthesia in all patients except those receiving 10 mg. The maximum level of sensory block, Th5-Th7, was reached within 30 min with a median duration of 3.6-3.9 h. The motor block was more profound with increasing dose, but never lasted longer than the sensory block. The influence on heart rate and blood pressure was minor and atropine and ephedrine were needed in four patients. No clinically significant ECG-changes were detected and no arrhythmias were recorded. Oxygen saturation and respiratory rate did not decrease in a clinically significant way and were not affected by concomitant morphine given i.v. postoperatively. There were few side-effects, the most frequent being mild pruritus (10/33). CONCLUSION: Sameridine provided clinically adequate anesthesia for the patients receiving the doses of 15, 20 and 25 mg. Further studies are needed to evaluate the substance and it is of great interest to clinically investigate the opioid component with respect to postoperative analgesia.

[Pain analysis is vital in rheumatic diseases. Pain often causes much worry to patients]. / Smärtanalys vital vid reumatiska sjukdomar. Smärtan oftast patientens största bekymmer.

The article consists of a synthesis of a rheumatic pain symposium held at the annual meeting of the Swedish Medical Association in 1996. Various aspects of pain in rheumatic diseases were discussed, such as physiological, neurohumoral and neurogenic mechanisms, sensory stimulation treatment, differentiation of mechanical and inflammatory pain, quality enhancement by improved co-operation between primary and tertiary care facilities, pharmacological treatment with (centrally and peripherally acting) opioids, selective cyclo-oxygenase inhibitors, and NMDA (N-methyl-D-aspartate) receptor antagonists. For patients with rheumatic disorders exacerbated by pain problems, as for other patients, a pain diagnosis is of fundamental importance. This can be achieved by analysis of the social, psychological, physiological and medical factors contributing to the cause and degree of pain and to pain behaviour, and of the extent to which the pain may be nociceptive (i.e., inflammatory, mechanical, or ischaemic in origin), neurogenic or idiopathic. Pain analysis should be followed by individualised treatment focused on the patient's most crucial problems, thus enhancing the prospect of optimal treatment outcome.

Obstetric outcome following epidural analgesia with bupivacaine-adrenaline 0.25% or bupivacaine 0.125% with sufentanil--a prospective randomized controlled study in 1000 parturients.

BACKGROUND: Epidural analgesia (EDA) is the most efficient method for pain relief during labour, but there is still a debate as to whether it interferes with the normal process of delivery. Some authors argue that the incidence of instrumental deliveries, Caesarean section, malrotation and protracted labour is increased in parturients receiving EDA. METHODS: 1000 parturients were prospectively randomized to receive EDA either with a high dose of local anaesthetic (0.25% bupivacaine with adrenaline = HD) or with a low dose (0.125% bupivacaine with sufentanil 10 micrograms = LD). RESULTS: The incidence of instrumental delivery and Caesarean section and the need for oxytocin was reduced in the LD compared to HD group. The delivery time was similar with HD and LD among primiparous, but decreased significantly among multiparous in the LD group. The incidence of malrotation was low in both groups. The quality of analgesia was equal during the first stage in the 2 groups, but was lower in the LD group during the second stage. More parturients in the LD group ambulated, but this did not affect the incidence of instrumental delivery. CONCLUSION: It is concluded that a lower dosage of bupivacaine combined with sufentanil in epidural analgesia significantly improves the obstetric outcome as compared to a higher dosage of bupivacaine with adrenaline using intermittent bolus technique.

[Pain analysis is vital in rheumatic diseases. The pain is often the patient's worst problem]. / Smärtanalys vital vid reumatiska sjukdomar. Smärtan oftast patientens största bekymmer.

The article consists of a synthesis of a rheumatic pain symposium held at the annual meeting of the Swedish Medical Association in 1996. Various aspects of pain in rheumatic diseases were discussed, such as physiological, neurohumoral and neurogenic mechanisms, sensory stimulation treatment, differentiation of mechanical and inflammatory pain, quality enhancement by improved cooperation between primary and tertiary care facilities, pharmacological treatment with (centrally and peripherally acting) opioids, selective cyclo-oxygenase inhibitors, and NMDA (N-methyl-D-aspartate) receptor antagonists. The aim of the symposium, with its focus on the manifest pain problem, was to improve our knowledge and skill in the understanding and treatment of this large patient category. For patients with rheumatic disorders exacerbated by pain problems, as for other patients, a pain diagnosis is of fundamental importance. This can be achieved by analysis of the social, psychological, physiological and medical factors contributing to the cause and degree of pain and to pain behaviour, and of the extent to which the pain may be nociceptive (i.e., inflammatory, mechanical, or ischaemic in origin), neurogenic or idiopathic. Pain analysis should be followed by individualised treatment focused on the patient's most crucial problems, thus enhancing the prospect of optimal treatment outcome.

Ropivacaine 7.5 mg/ml for elective caesarean section. A clinical and pharmacokinetic comparison of 150 mg and 187.5 mg.

BACKGROUND: The new, long-acting local anaesthetic ropivacaine has shown less systemic toxicity than bupivacaine and a concentration of 7.5 mg/ml can therefore be used for epidural anaesthesia in Caesarean section. The present pilot study was undertaken to find indications for an optimal dosage by comparing the clinical effects, quality of anaesthesia and pharmacokinetics of ropivacaine 150 mg (lower dose = LD) vs 187.5 mg (higher dose = HD) for women undergoing elective Caesarean section under epidural anaesthesia. METHODS: Sixteen full-term women scheduled for elective Caesarean section in two equal-sized consecutive groups received 20 or 25 ml ropivacaine epidurally in this non-randomised, open study. Study parameters included sensory and motor blockade, circulatory response, intraoperative pain and discomfort, neonatal evaluation and pharmacokinetic determinations. RESULTS: Block height varied between T5 and T2 in the LD group, whereas the HD group produced 4 unnecessarily high blocks (C8 in 3 women and C7 in 1 woman). Surgical anaesthesia was excellent in both groups. Circulatory stability was pronounced in the LD group (no ephedrine given), while 4 women required ephedrine in the HD group. Neonatal outcome as judged by Apgar scores; umbilical blood gas determinations and NACS scores were excellent in both groups. The plasma concentration-time profiles indicated linearity in the concentration range studied, with similar clearance values to those reported previously. Placental drug equilibrium was rapid; however, the foetal drug exposure depended on intrauterine exposure time. CONCLUSIONS: 20-25 ml ropivacaine 7.5 mg/ml produced very satisfactory conditions for elective Caesarean section under epidural anaesthesia. In this small population, 150 mg ropivacaine seemed optimal, while 187.5 mg produced unnecessarily extended block height in 50% of the women.

Effects of prostaglandin treatment and paracervical blockade on postoperative pain in patients undergoing first trimester abortion in general anesthesia.

BACKGROUND: The postoperative analgesic efficacy of a paracervical blockade (PCB) as an adjunct to general anesthesia (GA) during outpatient abortion (dilatation and curettage) is unclear, and the present study was initiated to evaluate if PCB is of significant importance per- or postoperatively. METHODS: Two hundred women (aged 18-49 years) were assigned to one of four groups; group 1 received vaginal prostaglandin (PG) (PGE1, gemeprost 1 mg) for softening of the cervix preoperatively and surgery was performed in GA, group 2 received preoperative PG and surgery was performed in GA + PCB; group 3 did not receive PG treatment and surgery was performed in GA and group 4 were subjected to GA + PCB without preoperative PG. RESULTS: Women receiving preoperative prostaglandin treatment (groups 1 and 2) reported significantly higher pain intensity already preoperatively, but also postoperatively as compared to patients not treated with PG. The patients subjected to prostaglandin treatment (groups 1 and 2) also had a significantly higher consumption of analgesics as compared to non-PG treated groups (3 and 4). The addition of PCB did not influence pre- and postoperative pain intensity significantly or consumption of analgesics. Patients receiving PG also reported significantly more nausea than the others although nausea was of low intensity. Patients receiving PG were, however, discharged earlier than the others from the hospital. CONCLUSIONS: Preoperative treatment of the cervix with prostaglandins was associated with significantly higher pain intensity both pre- and postoperatively, and increased need for analgesics postoperatively and more intense nausea. PCB given just before surgery did not result in significant postoperative analgesia. More efficient techniques for pain control should be developed for women subjected to first trimester abortion with preoperative PG treatment.

Local anesthesia for arthroscopic surgery of the ankle using pethidine or prilocaine.

Investigation of the intraoperative and postoperative pain-reducing effect of pethidine (meperidine) as compared with local anesthetics given into the ankle joint was performed, in a comparative and double-blind fashion, in 20 patients subjected to arthroscopy of the ankle, diagnostic and surgical procedures. These patients were randomly assigned to one of two groups. Group A consisted of 10 patients receiving prilocaine 5% with adrenaline and the patients of group B received pethidine 5% with adrenaline intraarticularly. During arthroscopy, the patients reported on pain and discomfort using visual analog scales. Ratings did not differ between the two groups, but six patients would not have chosen the local anesthetic technique again. Postoperatively, all patients rated their pain and discomfort at rest and at movement (1, 2, 3, 5, 6, 8, and 24 hours and at three times during 2 following days). No differences were found between the two groups, except for pain at rest through the whole observation period when significant lower values for pethidine. There were no differences in use of analgesics between the two groups. The current study indicates that pethidine is a potential alternative to prilocaine in arthroscopy of the ankle.

Anesthetic quality during cesarean section following subarachnoid or epidural administration of bupivacaine with or without fentanyl.

BACKGROUND: It is often assumed that subarachnoid administration of local anesthetics produces a more profound blockade than epidural anesthesia. Furthermore, the addition of fentanyl has been reported to increase preferentially intraoperative analgesia. In the present study we set out to study these two issues in a randomized and controlled study with respect to perceived pain and discomfort during surgery and postoperative pain. METHODS: In the present study, 100 parturients subjected to elective cesarean section, 34 nullipara and 66 multipara, received one out of four combinations of the local anesthetic bupivacaine and the opioid fentanyl; group A--bupivacaine 12.5 mg + 10 micrograms fentanyl subarachnoidally, group B--bupivacaine 12.5 mg + saline subarachnoidally, group C--bupivacaine 100 mg + 100 micrograms fentanyl epidurally, group D--bupivacaine 100 mg + saline epidurally; N = 25 in each group. Pain intensity and discomfort during surgery was assessed with a visual analogue scale (VAS). Postoperative pain intensity and need for analgesics postoperatively, ketobemidone, was registered for 24 h following surgery. RESULTS: Intraoperative pain intensity and discomfort did not differ significantly between parturients in any of the four groups Postoperative pain was significantly more intense in parturients receiving local anesthetics subarachnoidally as compared to the epidural groups during the first 6-h period. This difference was also reflected in a significantly increased consumption of analgesics during this period. No significant differences between the groups were observed with regard to hemodynamics (blood pressure), respiration (oxygen saturation) or other effects such as nausea or itching. All neonates had normal Apgar and neonatal adaptive capacity scores (NACS). CONCLUSION: We conclude that subarachnoidal (12.5 mg) and epidural (100 mg) injections with bupivacaine both produced adequate anesthetic quality in women undergoing elective cesarean section. The addition of fentanyl (10 micrograms subarachnoidally or 100 micrograms epidurally) did not significantly improve the quality of these already profound blockades.

Increased cerebrospinal fluid concentration of aspartate but decreased concentration of nitric oxide breakdown products in women experiencing visceral pain during active labour.

The aim of the present study was to investigate some putative neurotransmitters involved in nociception and pain in parturients during active labour experiencing intense visceral pain. The concentration of the excitatory amino acid aspartate was significantly increased, and there was a tendency for an increase in glutamate, in lumbar cerebrospinal fluid (CSF) of parturients in active vaginal labour compared with control patients without pain subjected to elective caesarean section. The CSF concentration of the nitric oxide breakdown product nitrate was significantly decreased in parturients compared with control patients and healthy volunteers. No significant differences in the concentrations of substance P, substance P-endopeptidase or met-enkephalin were detected between parturients and controls. Our data suggest a paradoxical negative relationship between CSF concentrations of excitatory amino acids and nitric oxide in labour pain. The mechanisms behind this finding is unclear at present.

Post-partum urinary retention: a comparison between two methods of epidural analgesia.

OBJECTIVE: To compare two methods of epidural labor analgesia regarding the incidence of post-partum urinary retention. STUDY DESIGN: One thousand parturients who requested epidural analgesia for the relief of labor pain received, at random, either bupivacaine 0.25% with adrenaline 1:200 000 (n = 500) or bupivacaine 0.125% with 10 micrograms sufentanil (n = 500). During the same observation period all women with clinically significant urinary retention (> 500 ml, requiring indwelling catheter) were registered. RESULT: Altogether 30/3.364 parturients had clinically significant urinary retention. Twenty-seven of these had received epidural analgesia (EDA) (17 with bupivacaine/adrenaline and ten with bupivacaine/sufentanil, a non-significant differences). The number of parturients with urinary retention was highly increased following EDA (27/1000) as compared to those not receiving EDA (3/2364), P < 0.001 (Fisher's exact test). In patients with EDA and urinary retention there were no difference between the groups in the incidence of instrumental deliveries or vaginal/perirectal tears. All parturients regained normal bladder function. CONCLUSION: EDA significantly increased the risk of post-partum urinary retention but no difference was found between the two epidural techniques.

Analgesia following arthroscopy--a comparison of intra-articular morphine, pethidine and fentanyl.

It has recently been reported that morphine given in low doses intra-articularly can produce significant analgesia in patients undergoing arthroscopic knee joint surgery. Data are lacking on the effect of other opioids using a local approach for drug delivery. We studied the analgesic effect of intra-articular opioids in 70 patients, divided into 7 groups, subjected to arthroscopic knee surgery in general anesthesia. The dimension of the study was based on a power of 0.8 to detect a 25% difference in pain intensity between those receiving opioids locally versus systemically (alpha = 0.05 and beta = 0.20). Following surgery, but before terminating anesthesia, the patients received one of the following combinations: 1 mg morphine intra-articularly (i.art.) + saline intramuscularly (i.m.), 10 mg pethidine i.art + saline i.m., or 10 micrograms fentanyl i.art + saline i.m. In three additional groups the three opioids were given i.m. and saline given i.art. An additional control group received saline i.art. + i.m. We did not find any significant difference between the groups considering postoperative pain intensity, need for analgesics or considering time to standing/walking or to discharge, analysing each opioid independently. There was, however, a tendency for pethidine i.art. to produce the lowest pain scores both at rest and during movement (P = 0.06). If analysing the results with regards to if opioids were given intra-articularly or systemically, not considering the type of opioid given, we did however, find a significantly lower total sum of pain scores at movement following local administration (P < 0.05). No specific side-effects were detected. We conclude that pethidine given intra-articularly merits further investigation with respect to postoperative analgesia following the activation of peripheral opioid mechanisms.

Lack of analgesic effect of systemically administered morphine or pethidine on labour pain.

OBJECTIVE: To evaluate the true analgesic effect of morphine and pethidine on labour pain. DESIGN: The analgesic and sedative effects of intravenous morphine or pethidine and their effect on anxiety were compared in a prospective, double-blind, randomised dose-response study. SETTING: A Stockholm teaching hospital obstetric unit. PARTICIPANTS: Ten healthy nulliparous parturients in active labour were included in each group. RESULTS: Even after repeated doses (up to 0.15 mg/kg body weight morphine and up to 1.5 mg/kg body weight pethidine) the findings were uniform, with very high pain scores maintained in each group as assessed with visual analogue scale. The parturients were all significantly sedated and several fell asleep but were awakened by pain during contractions. CONCLUSION: It is concluded that labour pain is not sensitive to systemically administered morphine or pethidine. These drugs only cause heavy sedation. It therefore seems unethical and medically incorrect to meet parturients' requests for pain relief by giving them sedation. Considering the well documented negative effects on newborn infants we also believe systemic pethidine should be avoided in labour.

Peroperative adenosine infusion reduces isoflurane concentrations during general anesthesia for shoulder surgery.

BACKGROUND: Adenosine (ADO), and stable analogs thereof, have been shown to exert antinociceptive action under experimental conditions in animals and in humans. The aim of this randomized double-blind placebo-controlled study was to evaluate if a low dose of intravenous (i.v.) ADO could reduce isoflurane requirements during joint-associated surgery, as an indication of antinociception in deep somatic pain. METHODS: Thirty-two patients, age 19-62 years, ASA I and II, scheduled for shoulder joint surgery, were assigned to receive an i.v. infusion of either adenosine, 80 micrograms.kg-1.min-1, or placebo, during the surgical procedure. Anesthesia was maintained with isoflurane/N2O/O2 inhalation. RESULTS: The peroperative isoflurane concentration was significantly reduced at 50 minutes of surgery in the group receiving adenosine infusion. Also, the systolic blood pressure level was peroperatively more stable during adenosine infusion than during placebo. Other clinical parameters, such as pain, postoperative analgesic requirements and nausea, were not different between groups. CONCLUSION: A peroperative infusion of a low dose of adenosine during shoulder joint surgery may reduce the peroperative isoflurane requirement.

Analgesic efficacy of intravenous morphine in labour pain: a reappraisal.

The aim of the present study was to investigate the dose-related analgesic effect of intravenous (i.v.) morphine during spontaneous term first stage labour. This was an open study in 17 parturients who requested analgesia for severe labour pain. All women were given morphine i.v. in repeated doses of 0.05 mg/kg following every third contraction until a final dose of 0.20 mg/kg was reached. The decrease in overall pain intensity, from median visual analogue scale (VAS) 85 (range 52-100) to median VAS 70 (range 46-99), was clinically insignificant. The number of women experiencing back pain, however, decreased significantly following morphine. The most striking effect of morphine (7.2-18 mg) was pronounced sedation. No adverse reactions related to morphine were noted in the neonates. We conclude that i.v. morphine does not significantly reduce overall labour pain intensity. Thus, if a real analgesic effect is desired, systemically given morphine seems inappropriate and other techniques should be used.

Effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and concentrations of neuropeptides in the hippocampus in WKY and SHR rats.

The effects of repeated sensory stimulation (electro-acupuncture) and physical exercise (running) on open-field behaviour and on hippocampal concentrations of neuropeptide Y, neurokinin A, substance P, galanin and vasoactive intestinal peptide (VIP)-like immunoreactivities were studied in WKY (wistar-Kyoto) and SHR (spontaneously hypertensive) rats. Significantly higher concentrations of substance P-like immunoreactivity, neurokinin A-like immunoreactivity and neuropeptide Y-like immunoreactivity were found in the hippocampus immediately after 3 weeks of treatment (electro-acupuncture and running), but not 1 week after the last (tenth) changes in neuropeptide concentrations were similar in the two rat strains. Open-field behaviour was significantly reduced during the treatment period in both strains. There were significant negative correlations between behaviour and neuropeptide concentrations in SHR rats, suggesting interdependency with sympathetic activity. It is proposed that the effects of electro-acupuncture and physical exercise in rats are related to increases in neuropeptide Y, neurokinin A and substance P in the hippocampus.

Sympathectomy does not influence experimental itch and cutaneous temperature perception thresholds.

The effect of endoscopic thoracic sympathectomy on experimentally histamine-induced itch was studied in seven patients, all of whom were suffering from palmar hyperhidrosis; cutaneous warm, cold, and heat pain perception thresholds were also studied in five of these seven patients. Surgery was effective in abolishing palmar sweating in all patients. No significant differences were seen in itch, flare, wheal, or thermal perception thresholds following sympathectomy as compared to the preoperative period. These findings suggest that the sympathetic system may be of limited importance for somatosensory perception in healthy humans during normal conditions.