[Piritramide : A critical review]. / Piritramid : Eine kritische Übersicht.

BACKGROUND: In many European countries and particularly in Germany, piritramide is the first choice opioid analgesic for the management of postoperative and posttraumatic pain. OBJECTIVE: The aim of this study was to review the pharmacological properties of piritramide and to evaluate whether these result in any clinical advantages with respect to effectiveness, safety and side effect profile compared to other strong opioids. MATERIAL AND METHODS: A systematic literature search was conducted in PubMed and Google Scholar and 27 articles published between 1961 and 2015 were retrieved and included in this review. RESULTS: Piritramide is a strong opioid that can only be administered parenterally. After intravenous injection it is effective after 17 min with pain relief lasting for up to 6 h. It is metabolized in the liver to inactive compounds, which is advantageous compared to morphine where active metabolites can accumulate in patients with renal failure. Piritramide is highly lipophilic resulting in a long context-sensitive half-life, making it unsuitable for continuous infusions. Studies further suggest that the side effect profile of piritramide is comparable to morphine. CONCLUSION: So far there is little evidence to support the widespread use of piritramide as first-line opioid analgesic for postoperative pain management in Germany. Especially lacking are in-depth studies about its mechanisms of action, receptor pharmacology, dose-response relationships and clinical dosing regimens. It is therefore questionable why piritramide is given priority.

[Piritramide versus oxycodone for patient-controlled intravenous analgesia. Opioid-induced side effects]. / Patientenkontrollierte i.v.-Analgesie mit Piritramid vs. Oxycodon. Opiatinduzierte Nebenwirkungen.

BACKGROUND: The aim of the study was to compare the opioid piritramide (7.5 mg/ml) which is commonly used in Germany (equipotential 5 mg morphine) to oxycodone (10 mg/ml) when given for patient-controlled intravenous analgesia (PCIA) in surgical disciplines, such as general surgery, orthopedic surgery, trauma surgery and gynecological surgery. Typical side effects of the respective opioids and safety of the procedures were compared. Oxycodone is available both as parenteral and oral formulations. MATERIALS AND METHODS: Data from the acute pain service during patient-controlled analgesia were evaluated. Quantitative data regarding opioid consumption and typical opioid side effects as well as qualitative results of patient satisfaction were recorded and evaluated for the respective specialist disciplines. RESULTS: Between 1 April 2005 and 31 August 2007 (35 months) 2,231 patients were treated with piritramide PCIA (PPCIA) and between 1 September 2007 and 31 December 2012 (64 months) 4,714 patients were treated with oxycodone PCIA (OPCIA). Patient satisfaction: overall, patients in both groups rated PCIA as very good or good with a higher percentage (98.9 %) in the oxycodone group than in the piritramide group (96.7 %) and 0.3 % of patients were only moderately satisfied or dissatisfied with the therapy. Typical side effects of opioids: the rate of side effects in the oxycodone group (6.7 %) was approximately 50 % lower compared with the piritramide treatment group (12.7 %). Nausea: with approximately 4 % in the piritramide group across all 4 specialties the incidence of nausea was markedly higher in the piritramide group than in the oxycodone group; however, this difference was statistically significant only for general and orthopedic surgery. Vomiting: vomiting was reported in about 6 % (mean) for PPCIA and significantly less frequently in 2 % (mean) for OPCIA. Fatigue and somnolence: these two side effects typically seen with opioid PCIA occurred only very rarely in a total of 1 % of all patients. In the PPCIA group the incidence was 1 % as directly compared to the significantly lower incidence of 0.6 % in the OPCIA group. CONCLUSION: The direct comparison of piritramide and oxycodone showed advantages for oxycodone in terms of typical opioid side effects. The effectiveness of analgesia was comparable in both groups.

Efficacy of intravenous paracetamol compared to dipyrone and parecoxib for postoperative pain management after minor-to-intermediate surgery: a randomised, double-blind trial.

BACKGROUND AND OBJECTIVE: Paracetamol has a well established pharmacological profile, but its postoperative efficacy is in question. This double-blind, placebo-controlled study was designed to compare the efficacy of intravenous paracetamol with other intravenous non-opioids as part of a multimodal concept for perioperative pain therapy. METHODS: Patients undergoing minor-to-intermediate surgery under general anaesthesia were randomly assigned to receive infusions of paracetamol (1 g every 6 h), dipyrone (1 g every 6 h), parecoxib (40 mg every 12 h) separated by infusions of physiological saline 0.9%, or placebo (0.9% saline every 6 h), respectively, for at least 48 h as part of a multimodal pain concept. Patient-controlled piritramide was administered as rescue medication. Dependent variables were recorded 1, 6, 18, 30 and 42 h after extubation and 1 week after surgery. Surgical and associated pain was scored as the primary outcome on a visual analogue scale. Additionally, time to first dose and total piritramide dosage, satisfaction, respiratory depression, nausea, vomiting, sedation, itching and sweating were recorded. RESULTS: A total of 196 patients were recruited. The efficacy of paracetamol was similar to that of the other non-opioid analgesics. Surgical pain was reduced with all non-opioids compared to placebo; there was no effect on associated pain. Piritramide dosage and incidence of side effects were not reduced. CONCLUSION: Intravenous paracetamol has equivalent efficacy to non-opioids dipyrone and parecoxib that improves postoperative pain therapy when used as part of a multimodal concept after minor-to-intermediate surgery.

[Circadian rhythm of PCA-based opioid consumption in children with chemotherapy-related mucositis]. / Zirkadianer Rhythmus des PCA-gesteuerten Opioidverbrauchs bei Kindern mit chemotherapiebedingter Mukositis.

BACKGROUND: In order to match the interindividual and intraindividual differences in opioid requirements of pediatric oncology patients with mucositis, patient-controlled analgesia (PCA) seems to be the optimal pain therapy option, but scientific data are lacking. METHOD: A retrospective chart review of PCA-treated children with mucositis was carried out over a 6-year period (2000-2006) at the university hospital for children in Erlangen. RESULTS: The median age of the patients was 12.6 years and they mainly suffered from forms of acute leukemia. Daily morphine equivalent dose (MED) requirements increased with the start of the PCA therapy from 14.5 mg/day to 18.7 mg/day (p=0.021; Wilcoxon test). Children required more opioids by bolus request during the night (10:01 p.m. to 06:00 a.m.; 6.28 mg; 13%) than during the other 8-hour intervals (06:01 a.m. to 02:00 p.m. and 02:01 p.m. to 10:00 p.m.; both 21.3 mg (43.5%) during the whole 10-day study period. In 8 out of 10 days there was a significant diurnal variation in opioid requirement with significantly lower requirement during the night (p<0.05 Friedman test). The median count of delivered and un-delivered bolus requests during the night was 0-1 and 0, respectively. CONCLUSION: PCA seems to be an ideal, dependable and feasible mode of analgesic administration for the individual titration of dose in children with chemotherapy-induced mucositis. This is expressed through the increase in daily self-administered opioid doses after starting PCA, the huge interindividual variability in opioid consumption and the rare event of an un-delivered bolus request during lock-out time. With the use of a background infusion, additional bolus requests are rare during the night.

Intrathecal Morphine for Laparoscopic Segmental Colonic Resection as Part of an Enhanced Recovery Protocol: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Management of postoperative pain after laparoscopic segmental colonic resections remains controversial. We compared 2 methods of analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of the study was to investigate whether administration of intrathecal bupivacaine/morphine would lead to an enhanced recovery. METHODS: A single-center, randomized, double-blind controlled trial was performed (NL43488.101.13). Patients scheduled for laparoscopic segmental intestinal resections were considered. Exclusion criteria were patients in whom contraindications to spinal anesthesia were present, conversion to open surgery, and gastric and rectal surgery. The intervention group received single-shot intrathecal bupivacaine/morphine (12.5 mg/300 µg), with an altered dose for older patients. The control group received a sham procedure and a bolus of piritramide (0.1 mg/kg). Both groups received standardized general anesthesia and a patient-controlled intravenous analgesia pump as postoperative analgesia. All patients were treated according to an ERAS protocol. A decrease in days to "fit for discharge" was the primary outcome. RESULTS: Fifty-six patients were enrolled. Intervention group patients were fit for discharge earlier (median of 3 vs 4 days, P = 0.044). Furthermore, there was a significant decrease in opioid use and lower pain scores on the first postoperative day in the intervention group. There were no differences in adverse events (except for more pruritus), time to mobilization, fluid administration, or patient satisfaction. CONCLUSIONS: This randomized controlled trial shows that intrathecal morphine is a more effective method of postoperative analgesia in laparoscopic surgery than intravenous opioids within an ERAS program. Recovery is faster and less painful with intrathecal morphine. Other studies have confirmed these results, although data on faster recovery are new and require confirmation in future trials. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, identifier NCT02284282.

[Analgesia in colon surgery. Can the use of NSAIDs reduce the opioid consumption following conventional and laparoscopic interventions?]. / Analgesie in der Kolonchirurgie. Kann die Verwendung von Nichtopoidanalgetika den Opioidbedarf nach konventioneller und laparoskopischer Kolonchirurgie senken?

BACKGROUND: The goal of our study was to evaluate the morphine-sparing effect of nonsteroidal anti-inflammatory drugs (NSAIDs) following both conventional and laparoscopic colon surgery. MATERIALS AND METHODS: In this prospective, randomized clinical trial, 180 patients were assigned to three groups. Two groups received either paracetamol or parecoxib/valdecoxib in addition to piritramid via patient-controlled or nurse-controlled analgesia pump. Patients in the control group received piritramid only. The total piritramid consumption during hospital stay was recorded. RESULTS: Total opioid consumption was significantly lower in the two groups who received NSAIDs. Comparing conventional and laparoscopic surgery, the latter group had much lower opioid consumption. CONCLUSION: The use of NSAIDs following colon surgery significantly reduces postoperative opioid consumption.

Auricular acupuncture for pain relief after total hip arthroplasty - a randomized controlled study.

Auricular acupuncture (AA) is known to be effective in treatment of various pain conditions, but still there have been no randomized controlled studies of AA for treatment of acute postoperative pain. Therefore we tested whether AA of specific points is superior to sham acupuncture for complementary analgesia after total hip arthroplasty in a patient-anesthesiologist-evaluator-analyst blinded study. The patients were randomly allocated to receive true AA (lung, shenmen, thalamus and hip points) or sham procedure (4 non-acupuncture points on the auricular helix). Permanent press AA needles were retained in situ 3 days after surgery. Postoperative pain was treated with intravenous piritramide (opioid receptor agonist with analgesic potency of 0.7 compared with morphine) using a patient-controlled analgesia (PCA) pump. The time to the first analgesic request, the amount of postoperative piritramide via PCA and pain intensity on a 100-mm visual analogue scale (VAS-100) were used to evaluate postoperative analgesia. Intraoperative anesthetic requirement, incidence of analgesia-related side effects, inflammation parameters and success of patients' blinding were also recorded. Fifty-four patients (29 AA and 25 controls) completed the study. Piritramide requirement during 36 h after surgery in AA group was lower than in control: 37+/-18 vs. 54+/-21 mg; mean+/-SD; P=0.004. Pain intensity on VAS-100 and incidence of analgesia-related side effects were similar in both groups. The differences between the groups as regard patients' opinions concerning success of blinding were not significant. Findings from our study demonstrate that AA could be used to reduce postoperative analgesic requirement.

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.

Effect of pre-emptive hydromorphone administration on postoperative pain relief--a randomized controlled trial.

BACKGROUND AND AIM OF STUDY: Pre-emptive analgesia represents a treatment strategy which tries to prevent the development of pain by inhibiting central reactions to peripheral sensory stimuli. In a prospective randomized double-blind placebo-controlled study, the effect of oral premedication with 4 mg of a slow-release hydromorphone preparation on postoperative piritramide consumption and subjective pain perception is being evaluated. PATIENTS AND METHODS: 96 women undergoing hysterectomy were randomly assigned to four study groups. Patients from groups 1 and 2 received hydromorphone and placebo respectively two hours before surgery, while those from groups 3 and 4 were given the same substances one hour after the end of the operation. Postoperative pain relief was provided by a patient-controlled infusion pump with piritramide. The intensity of postoperative pain as perceived by the patients was quantified on a visual analogue scale. Piritramide consumption and pain scores were recorded at 1 and 24 hours after surgery. Approval of the local Ethics Committee had been obtained beforehand as well as written informed consent from the patients. RESULTS: No significant differences in piritramide consumption were observed in between the four study groups. Visual analogue scale (VAS) ratings at 1 and 24 hours after surgery did not show any significant differences either--irrespective of whether the patients had received hydromorphone or placebo preoperatively or postoperatively. CONCLUSION: In our study, oral administration of 4 mg of slow-release hydromorphone did not show any greater pre-emptive analgesic effect than placebo.

[Long-term experiences with mechanical patient-controlled analgesia pumps for therapy of postoperative pain in general surgery]. / Langzeiterfahrungen in der Anwendung mechanischer PCA-Pumpen zur Therapie postoperativer Schmerzen in der Allgemeinchirurgie.

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.

[Patient-controlled analgesia (PCA) for postoperative pain relief. A prospective observational study for evaluating the technology in a ward routine]. / Patientenkontrollierte Analgesie (PCA) zur postoperativen Schmerztherapie. Eine prospektive Beobachtungsstudie zur Technologiebewertung im Stationsbetrieb.

Patient-controlled analgesia (PCA) is rarely used on surgical wards despite described advantages of this method as compared to conventional techniques. Uncertainties in patient selection and insufficient evaluation of this technique may explain these circumstances. The aim of our study was to evaluate PCA on general surgery and traumatology wards by means of standardized criteria for technology assessment (i.e. safety, practicability, benefit for patients and medical staff) and the efficacy of pain relief. In a prospective study we investigated 120 patients. In phase I, we performed analgesic therapy with tramadol/metamizol (50 ASA status I-IV patients). In phase II, piritramid had been applied to 70 ASA status I-II patients after an intermediate analysis of phase I. In 7% of the patients technical problems led to an early interruption even at the end of the study period. There were, however, no incidents which caused vital problems for the patients. A mean postoperative pain level of 55 visual analogue scale points (0-100 point scale) was achieved with tramadol/metamizol. PCA was stopped in 16% of the patients due to the occurrence of nausea or vomiting and in two patients due to insufficient pain relief. The use of piritramid in phase II led to lower pain levels and no interruptions of PCA because of ineffectivity or nausea/vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

[Postoperative pain therapy in urology. A prospective study]. / Postoperative Schmerztherapie in der Urologie. Eine prospektive Studie.

A sufficient analgesic treatment in the early postoperative period is important for the patients comfort level. Moreover, physical therapy for prophylaxis of pneumonia and thrombosis is better tolerated. In a prospective study, we compared two postoperative pain management regimens to establish a sufficient pain management without the need of additional costs or manpower. Of 215 patients undergoing major urologic surgery, 111 patients received on demand medication exclusively (group 1), whereas 104 patients were treated with basic analgesics combined with on demand medication (group 2). Pain intensity, side effects and subjective well being were evaluated with a visual analogue scale and a standardised interview. Pain intensity and side effects were significantly lower in group 2. Thus, with combined analgesic treatment, postoperative pain relieve can be achieved safely and without additional costs.

Percutaneous balloon kyphoplasty with the patient under intravenous analgesia and sedation: a feasibility study.

BACKGROUND AND PURPOSE: Kyphoplasty is a minimally invasive procedure for the treatment of malignant or osteoporotic vertebral compression fractures, normally performed with the patient under general anesthesia. This may cause a therapeutic dilemma because these patients often have a very high risk for general anesthesia due to concomitant diseases. The aim of this study was to evaluate the safety and feasibility of percutaneous kyphoplasty by using IV anesthesia and sedation with midazolam and piritramide. MATERIALS AND METHODS: From June 2007 to June 2009, we prospectively included 133 patients (77 women, 56 men; mean age, 69.18 ± 11.45 years) who were referred for BKP. Kyphoplasty was always performed under fluoroscopic guidance with a biplane angiographic system by using a transpedicular or extrapedicular approach. The individual anesthesia risk was assessed by using the ASA criteria. All procedures were performed with the patient under IV anesthesia and sedation with fractionated administration of midazolam and piritramide. Pain was assessed before and after treatment by using a VAS. RESULTS: Ninety-nine patients (74.4%) had a significantly increased risk for general anesthesia (ASA score, ≥ 3). A total of 162 kyphoplasty procedures were performed. The mean amounts of midazolam and piritramide used were 11.3 ± 4.38 mg and 11.8 ± 3.98 mg, respectively. No complications related to IV anesthesia and sedation occurred. Periprocedural pain management was rated as sufficient, and all patients would undergo the procedure again. CONCLUSIONS: Percutaneous BKP with the patient under IV anesthesia and sedation with midazolam and piritramide is a safe and feasible method for treating vertebral compression fractures in patients with an increased risk for general anesthesia.