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Focal myopathy associated with chronic intramuscular injection of piritramide.

We report a patient in whom chronic intramuscular piritramide led to a focal fibrotic myopathy. Since piritramide myotoxicity has never been reported, we have studied its effect on rat skeletal muscle. Chronic intramuscular piritramide led to fibrous connective tissue replacement of rat skeletal muscle, similar to that found in the patient's muscle. Although the pathogenetic mechanism of piritramide myopathy is unclear, we caution against prolonged intramuscular use of piritramide to prevent this potentially debilitating adverse effect.

Adult↗

[Patient-controlled analgesia with clonidine and piritramide].

UNLABELLED: Following parenteral administration, clonidine has analgesic effects at both cerebral and spinal levels. Patient-controlled analgesia (PCA) makes it possible to determine equipotent dosages of analgesics by relating analgesic consumption per time to the levels of analgesia obtained in comparable patient populations. Therefore, we studied the equipotency ratios of clonidine and piritramide and the incidence of undesired side effects in the treatment of postoperative pain in patients undergoing maxillo-facial surgery. METHODS: After approval of the local ethics committee and informed consent 40 patients (age > 18 year, ASA I-III) were studied. Following randomization, the patients each received a PCA device containing either clonidine (bolus 30 micrograms), or piritramide (bolus 1.5 mg) for treatment of postoperative pain (lockout interval 5 min in both groups). During the postoperative period, pain was determined using a visual analogue scale, while analgesic consumption, sedation, haemodynamic parameters, respiration rate, and the occurrence of undesired side effects were documented additionally. RESULTS: The groups had comparable distributions of biometric data, duration of anaesthesia, and ASA classification. Pain level decreased significantly (P < 0.0001) in both groups during the first 2 h of PCA. Mean arterial pressure and heart rate were lower (P < 0.05) in the clonidine group 4 and 6 h after PCA onset, while the degree of sedation after 2 (P < 0.01) and 6 (P < 0.05) h was higher than in the piritramide group. Nausea and vomiting were more frequent (P < 0.05) in the piritramide group. Both groups showed a wide interpatient variation in analgesic requirement. The equipotency ratio clonidine/piritramid was 1:63.7. CONCLUSION: Intravenous clonidine is a potent analgesic and is suitable or the treatment of postoperative pain following maxillo-facial surgery. The analgesic potency of 150 micrograms clonidine i.v. was equivalent to that of 9.56 mg piritramide i.v. Nausea and vomiting occurred more rarely in the clonidine group, while deeper sedation was observed more frequently than in the piritramide group. Owing to the wide interindividual variation of analgesic consumption, clonidine dosages have to be adjusted to the actual requirements.

Adolescent↗

[Patient-controlled analgesia. PCA in a three year old child after traumatic amputation].

We report the case of a 3-year-old boy, who received long-term parent-controlled analgesia after traumatic amputation of one leg. He underwent surgery 17 times for a period of 25 days. Parent-controlled analgesia was started four days after admission because analgesia with non-opioid analgetics (acetaminophen) proved to be insufficient. The pump was set to a bolus-dose of 23 micrograms kg-1 piritramide (dipidolor) and a lockout interval of 10 minutes. Permitted maximum cumulative dose in four hours was 5 mg piritramide. There was no continuous infusion of opioid. PCA and possible adverse effects were explained to the mother. A monitoring regimen was used to assess efficacy (pain intensity estimated by the mother), adverse effects (sedation score, occurrence of nausea and vomiting) and piritramide consumption. For fear of side effects opioid administration was insufficient in the beginning. After three days the mother used the PCA effectively and no additional analgesic medication was required. Nausea or other side effects were not observed. After seven days opioid consumption nearly doubled. Apart from tolerance, this might have resulted from the mother's caution in the first days. After 17 days the PCA was discontinued. Oral analgetics (tramadol) controlled the pain adequately. Management of postoperative pain in children is difficult and too often insufficient. PCA is a safe and effective method of providing postoperative pain relief. Feasibility was shown in adolescents and, more recently, in children aged five years and over. Only few reports are available describing long term use of PCA in children younger than five years. Our case suggests that PCA may also be used effectively and safely in children younger than five years, if experienced staff, a monitoring regimen and cooperative and well instructed parents are available.

Amputation, Traumatic↗

[Long-term experiences with mechanical patient-controlled analgesia pumps for therapy of postoperative pain in general surgery].

The efficiency and safety of patient-controlled analgesia (PCA) in the treatment of postoperative pain is well documented. An alternative to electrical systems is the disposable pump, which is cost effective. The aim of this study was to prove the efficiency and safety of PCA disposable pumps. Eighty patients (45 men, 35 women, mean age 50 +/- 16 years) were included and received single-use PCA pumps (Vygon Medical Products, Aachen, Germany) for postoperative pain control. A sufficient reduction in pain levels, measured by the Verbal Rating scale (VRS), was achieved in nearly all patients. For the first application, a single bolus of 7.0 +/- 2 mg piritramide (Dipidolor) was needed, the mean of treatment time was 56 +/- 31 h. We had two dropouts because of non-compliance, two patients felt dizzy, and one patient felt nauseous. Further side-effects were observed during treatment. Our study led us concluded that PCA therapy with mechanical, disposable pumps is a safe and efficient treatment for postoperative pain. Such a concept can be introduced without an "Acute Pain Service" if the staff are well trained.

Adolescent↗

[Pain therapy after thoracoscopic interventions. Do regional analgesia techniques (intercostal block or interpleural analgesia) have advantages over intravenous patient-controlled opioid analgesia (PCA)?].

Systemic opioids and thoracic epidural analgesia are common techniques used to provide post-operative analgesia following thoracoscopy (video-assisted thoracic surgery). The aim of the present prospective randomised study was to evaluate the efficacy of two less invasive analgesic techniques, intercostal blocks (ICB) and interpleural analgesia (IPA). After approval from the ethics committee and informed consent from the patients, 36 patients scheduled for thoracoscopic surgery were randomly assigned to a group for postoperative pain management: group ICB: intercostal blocks of the segments involved with 5 ml 0.5% bupivacaine at the end of surgery and 6 h later; group IPA: interpleural analgesia with 20 ml 0.25% bupivacaine applied every 4 h using a catheter placed during surgery near the apex of the interpleural space; control group: IV-opiod-PCA with piritamide. Patients in the ICB and IPA groups had access to pain relief by PCA with piritramide as well. Additional medication for all groups if the analgesia was insufficient consisted of metamizol. There were no significant differences in piritramide consumption between the two regional analgesia groups and the control group up to the 3rd and 7th postoperative day. Up to the 7th day piritramide consumption in group ICB was 78 mg, in group IPA 75 mg and 80 mg in the control group. Patients in group ICB showed significantly less pain at rest measured by the visual analogue scale (VAS) on the 1st postoperative day (U-test, P < 0.05), but otherwise there were no statistical differences regarding pain scores. Respiratory parameters such as forced vital capacity, forced expiratory volume, peak flow and the Tiffeneau test (FVC, FEV1, PF, FEV1/FVC) were reduced significantly after thoracoscopy and showed a slow recovery in all three groups without significant intergroup differences. Thoracoscopic surgery causes less and shorter lasting pain in comparison to thoracotomy. Nevertheless, effective pain management is necessary. We could not demonstrate a significant reduction in piritramide consumption for the techniques of regional analgesia tested here (ICB, IPA). We conclude that the use of these techniques is not complementary after thoracoscopy, since an opioid (PCA with piritramide) combined with a non-opioid (metamizol) resulted in satisfactory analgesia.

Adult↗

Protein binding of piritramide: influence of various protein concentrations and the postoperative acute phase response.

OBJECTIVE: Piritramide is a lipophilic opioid, which is widely used for postoperative analgesia and analgosedation in Europe. In this study we investigated the influence of various protein concentrations (total protein, alpha1-acid glycoprotein, albumin) and the postoperative acute phase response on the protein binding of piritramide. METHODS: The influence of various protein concentrations on the protein binding of piritramide was investigated by either diluting the serum samples of five volunteers with isotonic saline or by adding different amounts of alpha1-acid glycoprotein. Albumin binding was measured in a 5% human albumin solution. The impact of the postoperative acute phase response was investigated by obtaining daily serum samples from 18 surgical patients until the third postoperative day, and measuring piritramide protein binding, alpha1-acid glycoprotein, total protein and albumin. RESULTS: There was a significant relationship between piritramide protein binding and the concentrations of total protein and alpha1-acid glycoprotein. The binding to albumin was 88%. During the postoperative acute phase response, the protein binding of piritramide did not change. Serum concentrations of alpha1-acid glycoprotein increased, whereas total protein and albumin decreased. CONCLUSION: Although there were significant changes in the piritramide-binding proteins, alpha1-acid glycoprotein and albumin, during the postoperative acute phase response, the protein binding of piritramide did not change. Therefore, a change in protein binding, which might be one factor to be considered in determining piritramide dosage in the postoperative period, does not have to be taken into account.

Acute-Phase Reaction↗

Posterior retroperitoneoscopy as a new minimally invasive approach for adrenalectomy: results of 30 adrenalectomies in 27 patients.

Posterior retroperitoneoscopic adrenalectomy is a new minimally invasive method. It represents an alternative to conventional open procedures and laparoscopic techniques. Between July 1994 and November 1995 a total of 30 retroperitoneoscopic adrenalectomies were performed on 27 patients. In 24 patients, unilateral tumors were seen (size 1-7 cm): seven Cushing adenomas, five Conn adenomas, seven pheochromocytomas, four hormonally inactive tumors, one cyst. Three patients suffered from Cushing syndrome with bilateral adrenal gland hyperplasias (two inoperable pituitary gland tumors, one bronchial carcinoid with ACTH secretion). The operations were carried out in prone position. After balloon dilatation of the retroperitoneum and creation of a pneumoperitoneum the preparation of the adrenal gland was performed via three trocar sites positioned below the 12th rib. Twenty-five adrenalectomies were completed endoscopically, and five times (among four patients) conversion to the conventional posterior technique was necessary. The average operating time of complete endoscopic adrenalectomies was 124 minutes (45-225 minutes); blood loss was 10 to 120 ml. With minimal need for postoperative analgesia (average dosage 7.9 mg of piritramide), mobilization and adequate food uptake were possible on the day of operation. The posterior retroperitoneoscopic adrenalectomy is a relatively fast, safe method, with the advantages of the posterior open approach and minimally invasive surgery. It therefore represents an important addition to adrenal gland surgery.

Adenoma↗

Pain therapy following joint replacement.A randomized study of patient-controlled analgesia versus conventional pain therapy.

A prospective randomized trial in 42 patients undergoing elective total hip or knee arthroplasty under general anaesthesia was carried out to evaluate the efficacy of patient-controlled analgesia (PCA) versus demanded conventional pain therapy (CPT) for controlling postoperative pain. Four patients had to be excluded from the study (2 postoperative confusion, 1 elevated piritramid dosage caused by chronic pain therapy, 1 stressed by PCA pump handling). PCA group (n = 19) received piritramid via PCA pump, CPT group (n = 19) received tramadol (oral or intramuscularly) or piritramid intravenously. PCA or CPT was started in the intensive care unit. Pain was measured with a standard 100 mm visual analogue scale (VAS) for 60 h postoperatively. Over this period of time, no significant differences were found in the pain score of both groups, nor did the incidence of side-effects differ significantly. The PCA group required on average twice as much piritramid-equivalent than the CPT group (P < 0.001). Patient satisfaction was good in both groups, but significantly better in the PCA group (P < 0.01), although the measured postoperative individual pain scores were above the preoperatively determined individual subjective pain threshold in the majority of both groups. From these results we draw the conclusion that even if the patients feel satisfied by the pain therapy administered, the majority are objectively treated below their individual subjective pain threshold.

Administration, Oral↗

Sensitive determination of piritramide in human plasma by gas chromatography.

A selective and sensitive method for the determination of piritramide in human plasma is described. A 1-ml aliquot of plasma was extracted with 10 ml of hexane-isoamyl alcohol (99.5:0.5, v/v) (extraction efficiency 86%) after addition of 50 microliters of 2 M ammonia and 20 microliters of aqueous strychnine solution (100 ng per 10 microliters) as internal standard. Gas chromatography was performed with J&W DB-1, 30 m x 0.53 mm I.D. separation column, film thickness 1.5 microns, using an nitrogen-phosphorus-sensitive detector. The assay was linear in the concentration range 3.75-2250 ng/ml (r = 0.999), with a lower limit of detection of 1-2 ng/ml. The precision was determined using spiked plasma samples (10 and 50 ng/ml), with coefficients of variation of 3.5 and 3.1% (intra-day; n = 5) and 4.6 and 4.1% (inter-day; n = 4). In the range 3.75-150 ng/ml, the accuracy of the assay was 3.36%. The method was used for the determination of piritramide plasma concentrations in patients receiving intra- or post-operative analgesia.

Chromatography, Gas↗

Postoperative pain management and respiratory depression after thoracotomy: a comparison of intramuscular piritramide and intravenous patient-controlled analgesia using fentanyl or buprenorphine.

STUDY OBJECTIVE: To compare the analgesic efficacy of fentanyl, buprenorphine, and piritramide and to define the respiratory risk during conventional postoperative pain management and patient-controlled analgesia (PCA). DESIGN: Randomized, single-blind study. SETTING: Department of anesthesiology of an urban hospital. PATIENTS: Sixty patients (ASA) physical status II and III) recovering from unilateral thoracotomy performed under standardized general anesthesia including intercostal blockade. INTERVENTIONS: Patients were treated with intramuscular (IM) piritramide (7.5 to 15 mg as needed) or intravenous (IV) PCA with fentanyl (demand dose 34 micrograms) or buprenorphine (demand dose 80 micrograms) during the early postoperative period, using the On-Demand Analgesia Computer (ODAC, Janssen Scientific Instruments, Beerse, Belgium). MEASUREMENTS AND MAIN RESULTS: The mean postoperative observation period was 24 to 25 hours. During this time, patients requested 55.8 +/- 23.2 mg of piritramide, 1.04 +/- 0.54 mg of fentanyl, or 1.81 +/- 0.78 mg of buprenorphine. Analgesia in all groups was judged mostly good to excellent, with a preference for PCA. Side effects were only of minor intensity in all groups; euphoria or dysphoria occurred only with buprenorphine. Two patients using PCA and five patients having IM analgesia developed short periods of respiratory depression (respiratory rate less than or equal to 8 breaths/minute and/or oxygen (O2) desaturation less than or equal to 90%), which promptly responded to commands to breathe deeply. Respiration rates did not differ, and frequent arterial blood sampling showed normal mean partial pressures of oxygen (PO2) and carbon dioxide (PCO2) and arterial oxygen saturation (SaO2) in all subgroups. CONCLUSIONS: Opioid-induced respiratory depression occurred infrequently during postoperative pain management whether by conventional means or using PCA, even though high doses of opioid analgesics were required intermittently for adequate postoperative pain relief by either technique.

Analgesia, Patient-Controlled↗

Pain treatment after thoracotomy: is it a special problem?

BACKGROUND: Although it is frequently stated in the literature that thoracotomy is one of the most painful operative incisions, few data supporting this view are available. METHODS: Patients' postoperative pain experience can be assessed on the basis of their usage of patient-controlled analgesia. In a prospective trial the daily self-administered doses of analgesics in 55 patients within the first 4 days after posterolateral thoractomy were compared with those in 30 patients for the same number of days after median laparotomy. The visual analog scale was used as a second measure to evaluate postoperative pain. RESULTS: On the basis of patient-controlled analgesia usage on the first postoperative day and the visual analog scale score for the first 2 days, a small but significant difference between the two patient groups was found which showed that thoracotomy is less painful than median laparotomy. CONCLUSIONS: The common belief that posterolateral thoracotomy is a very painful operative access is not true. Therefore it is not necessary to use special techniques for postthoracotomy pain relief in these patients. Patient-controlled analgesia is sufficient for pain relief after major thoracic or abdominal incisions.

Adolescent↗

Treatment of pain in trauma patients with injuries of the upper limb.

Since preoperative pain therapy of a trauma patient did not play an outstanding role in the past, this article shall give information about the adequate treatment of such patients, which can be mainly divided into three phases: the prehospitalisation phase with stabilisation of the trauma patient, the early phase of hospitalisation with further stabilisation, diagnosis and surgery, and finally the postoperative phase with corresponding treatment. An optimal analgesic in the prehospitalisation phase should guarantee good analgesic effects, rapid onset and good controllability, simple handling and the opportunity to combine it with other medication. In addition, it should prevent a wide therapeutic range and the absence of side effects. Opioids and ketamine are available for acute pain therapy after trauma. The main opioids used are piritramide and pethidine, with piritramide acting as a sedative at the same time and with pethidine preventing the stronger analgesic effect. The intravenous use of ketamine has become established in trauma patients because of its excellent analgesia at subanaesthetic doses. Especially in multiple trauma patients, the indication for general anaesthesia with intubation should be established on a liberal basis. Nevertheless, for some patterns of injury regional techniques may be advantageous; therefore, this article describes the possible regional procedures (such as intravenous regional anaesthesia or block of peripheral nerves). Concerning the postoperative phase, an individual pain management can be guaranteed by systemic pharmacotherapy and regional catheter techniques, for example the brachial plexus blockade that results in a long period of free pain.

Analgesics, Opioid↗

RETRACTED: Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen.

OBJECTIVE: To compare standard nurse-based pain therapy with a patient-controlled analgesia (PCA) regimen. DESIGN: Prospective, randomized study. SETTING: Single-institutional, clinical investigation in an urban, university-affiliated hospital. PARTICIPANTS: Sixty patients undergoing elective first-time cardiac surgery were included. INTERVENTIONS: In 30 patients, a standard analgesic regimen was used, and in 30 patients, a PCA regimen was used. The perioperative and postoperative management was similar for all patients. MEASUREMENTS AND MAIN RESULTS: Degree of sedation, satisfaction, and pain (by visual analog scale [VAS]) was assessed within the first 3 postoperative days. Vital capacity (VC) and forced expiratory volume in 1 second (FEV1) were measured using a portable spirometry system. Cortisol and troponin T (TnT) plasma levels were also measured. The expectation of pain was similar in both groups, and the postoperative pain score was significantly lower in the PCA than in the standard group throughout the study period. Significantly more piritramid was used in the PCA (total, 75.6 +/- 33.4 mg) than in the standard group (total, 20.1 +/- 31.9 mg). VC and FEV1 were significantly lower in the standard group compared with the PCA patients. Cortisol and TnT plasma levels were similar in both groups. Frequency of side effects were similar for both groups. CONCLUSION: Because of the beneficial effects with regard to degree of pain and satisfaction, pain management using PCA systems can be recommended for cardiac surgery patients. It appears to be superior to standard nurse-based pain therapy.

Analgesia, Patient-Controlled↗

Postoperative pain control following remifentanil-based anaesthesia for major abdominal surgery.

Eighty patients undergoing major abdominal surgery using remifentanil-based anaesthesia were randomly allocated in a double-blind manner to receive an intravenous bolus of fentanyl, buprenorphine, morphine or piritramide 20 min before the end of surgery. A reduced dose was administered postoperatively when patients reported moderate pain. Subsequent analgesia was provided by patient-controlled analgesia (PCA). The mean time from the end of anaesthesia to spontaneous respiration was 9 +/- 5 min. At first pain assessment, 63% of patients reported no or mild pain; 80% of patients required the second opioid bolus, those receiving piritramide needed the bolus significantly later than patients receiving buprenorphine or fentanyl. First PCA requirement also occurred significantly later in the piritramide group. This technique provided effective postoperative pain relief and transition to routine PCA and did not compromise recovery.

Abdomen↗

Pharmaco-economic evaluation of a disposable patient-controlled analgesia device and intramuscular analgesia in surgical patients.

The present study contrasted the pharmaco-economics and analgesic efficacy of intramuscular (i.m.) opioid treatment with a parenteral disposable patient-controlled analgesia (PCA) system in two groups of 20 female patients (ASA I-II, aged 35-69 years) scheduled for abdominal hysterectomy. The PCA group received a continuous infusion of 1.5 mg h-1 piritramide, a mu-opioid receptor agonist, with incremental doses of 1.5 mg (lock-out interval = 15 min). The i.m. group received 0.3 mg kg-1 piritramide i.m. when requested by the patient with a minimum interval of 5 h. Pain intensity, sedation and the functional recovery of the patients were followed for 72 h post-operatively. The sum of pain intensity differences (SPID) was used as a measure of analgesic efficiency. Equipment and drug costs, and the demand on nursing time were recorded over 3 days post-operatively. The costs of PCA and i.m. therapies per patient were used to calculate the cost-benefit (cost of treatment vs. nursing time) and cost-effectiveness (cost of treatment vs. SPID) analyses. Both treatments initially provided comparable analgesia, but PCA was more efficient after 16 h and significantly reduced nursing time for pain treatment (PCA = 61 +/- 4 min, i.m. = 88 +/- 5 min; P < 0.001). Functional recovery was not different for either treatment. Cost analysis indicated a better cost-benefit ratio for the i.m. treatment (0.35 vs. 1.1 for PCA treatment), but a similar cost-effectiveness for both treatments (PCA = 1.9 Belgian Francs (BEF) unit-1 SPID; i.m. = 1.7 BEF unit-1 SPID).

Activities of Daily Living↗

[Postoperative pain in patients after conventional abdominal and endoscopic surgery hysterectomy--a comparative study].

The purpose of the present study is to determine differences in the postoperative character of pain between two study groups undergoing different techniques of hysterectomy. Therefore we examined 42 women. 21 women underwent combined laparoscopic and vaginal hysterectomy and 21 abdominal hysterectomies have been performed. All patients received on request Piritramid i.m. exclusively as an analgesic. The following factors have been included: 1. location of pain, 2. duration of pain, 3. maximum of pain, 4. analgesic requirements, 5. return to normal physical activities. With regard to our findings it seems to be certain that endoscopic operative hysterectomy compared to abdominal hysterectomy shows diminished duration of pain and reduction in the total amount of analgesic usage, as well as a shortened time to return to normal physical activities.

Analgesics, Opioid↗

On-demand analgesia with piritramide in children. A study on dosage specification and safety.

The results of this study show that postoperative patient-controlled pain therapy in children with piritramide is - in a similar way as with adults - a safe method involving a low incidence of side effects. A special pump parameter setting is required with larger bolus dose sizes and longer lockout intervals, not very different from the experience gained with adults, and which is based on other values than those recommended up to now with morphine for paediatric PCA. Side effects were rarely observed. The fear of respiratory depression constitutes no rational reason to deny the younger patients this form of analgesia provided that monitoring is guaranteed.

Adolescent↗