The beta-adrenergic receptor agonist, terbutaline, reduces UVB-induced mechanical sensitization in humans.

OBJECTIVES: Previously, we found in cultures of primary neurons and in animals that sensitized primary neurons can be desensitized by treatment with e.g. beta-adrenergic receptor agonists. We now tested whether also in human sensitization such as UVB-radiation induced sunburn-like hyperalgesia can be reduced by intradermal injection of the beta-adrenergic receptor agonist terbutaline. METHODS: In our prospective randomized study, 17 participants received an individual UVB dose to cause a defined local sunburn-like erythema at four locations, two on each forearm. Twenty-four hours later, the sensitized four areas were injected intradermally with terbutaline pH 4.3, terbutaline pH 7.0, saline pH 4.3 or saline pH 7.0, respectively. Pain thresholds were examined before and after induction of UVB-sensitization, and 15, 30 and 60 min after injection of the respective solution. Mechanical pain thresholds of the skin and of deeper tissues were determined by pinprick and pressure algometer measurements, respectively. RESULTS: UVB-irradiation decreased mechanical pain thresholds for pinprick and pressure algometer measurements demonstrating a successful sunburn-like sensitization. Intradermal injection of terbutaline pH 7.0 into the sensitized skin reduced the sensitization for all measured timepoints as determined by pinprick measurements. Pinprick measurements of sensitization were not reduced by injection of terbutaline pH 4.3, saline solution pH 7.0 or saline solution pH 4.3. Also, sensitization of deeper tissue nociceptors were not altered by any of the injections as measured with the pressure algometer. CONCLUSIONS: Similar to our cellular observations, also in humans beta-adrenergic agonists such as terbutaline can reduce the sensitization of primary neurons in the skin. SIGNIFICANCE: We previously showed in model systems that beta-adrenergic stimulation can not only sensitize but also desensitize nociceptors. Our study shows that also in humans beta-adrenergic agonists desensitize if injected into UVB-sensitized skin. This indicates an analgesic activity of adrenergic agonists in addition to their vasoconstrictory function.

[Anesthesia and pain management during pregnancy]. / Anästhesie und Schmerztherapie während der Schwangerschaft.

During the perioperative and postoperative care of pregnant women it is prudent to pay close attention to the changed physiology of these patients. The main principles of care are the preservation of maternal and fetal homeostasis as well as avoidance of any substances with toxic effects on the fetus. In order to provide pregnant patients with good quality care, all relevant disciplines should be involved as early as possible. Modern anesthetic drugs can be used as they seem to be without teratogenic effects. Adequate perioperative surveillance and assessment of the fetus is also important.The mainstay of pain management during pregnancy is the World Health Organization (WHO) pain ladder. It is of the utmost importance to use only substances without teratogenic or fetotoxic properties. Considering non-opioid drugs, the use of paracetamol is a viable option, whereas non-steroidal anti-inflammatory drugs (NSAID) should only be used with rigorous restrictions. Tramadol is a first-line drug when using opioids with low potency, whereas morphine can be used as an opioid with a higher potency after careful consideration of the risk-benefit ratio. If possible anticonvulsives should not be used as an adjunct in pain management during pregnancy. The use of thoroughly investigated antidepressants seems to be a better alternative. Apart from drug therapy it is important to use all available conservative pain treatment options.

[Cost minimization analysis in postoperative pain management : economic efficiency and effectiveness of two infusion pump systems]. / Kostenminimierungsanalyse in der postoperativen Schmerztherapie : Wirtschaftlichkeit und Effektivität von 2 Schmerzpumpensystemen.

BACKGROUND: Besides reliable efficacy and patient satisfaction, economic efficiency is becoming increasingly more important in postoperative pain management. AIM: The present study investigated the effectiveness of two pain pump systems and compared the running costs in treatment. MATERIAL AND METHODS: In this study 40 patients received an interscalene catheter prior to shoulder surgery. Postoperative pain management was provided via an electronic pump with patient-controlled analgesia (PCA) or a mechanical pump without PCA. Patients kept a pain log. After treatment they were interviewed about their satisfaction with the pump. In addition drug consumption, nursing material, staff time for handling and maintenance of the pumps and preparation of medications pro re nata were assessed. RESULTS: Postoperative pain levels and patient satisfaction were comparable in both groups. Economically, the electronic pump was more cost-effective than the electronic model for a duration of treatment of 1 and 2 days. With treatment duration of 2 days the costs of both pumps were equivalent; however, the PCA feature of the electronic pump allowed a reduced intake of systemic analgesics on demand. CONCLUSION: Both pain pump systems provide equally effective pain management, while the electronic model caused less costs. Both pumps offer advantages and disadvantages that should be considered based on local circumstantial demands.

[Ultrasound in interventional pain therapy]. / Ultraschall in der interventionellen Schmerztherapie.

Peripheral nerve blocks are currently performed relatively blind even in the most complex anatomical structures and physicians mostly rely on palpable anatomical landmarks on the surface. Ultrasound has become an indispensable part of the modern medical world and has long since found its way into almost all medical professions. More and more this trend also reaches interventional pain physicians as it is possible to accurately target structures, to track the needle course during the intervention and to visualize the spread of the local anesthetic. Another advantage compared to other radiological techniques is the profound radiation safety for patients as well as for personnel performing the intervention. A deep understanding of anatomy and its correlate in ultrasound images is one of the most important requirements for the successful use of these interventional techniques. Moreover, the safe performance of the procedure depends on the simultaneous hand-eye coordination. Nevertheless, despite the euphoria ultrasound technology should only be used in pain management with sufficient indications.

[Ultrasound in interventional pain therapy]. / Ultraschall in der interventionellen Schmerztherapie.

Peripheral nerve blocks are currently performed relatively blind even in the most complex anatomical structures and physicians mostly rely on palpable anatomical landmarks on the surface. Ultrasound has become an indispensable part of the modern medical world and has long since found its way into almost all medical professions. More and more this trend also reaches interventional pain physicians as it is possible to accurately target structures, to track the needle course during the intervention and to visualize the spread of the local anesthetic. Another advantage compared to other radiological techniques is the profound radiation safety for patients as well as for personnel performing the intervention. A deep understanding of anatomy and its correlate in ultrasound images is one of the most important requirements for the successful use of these interventional techniques. Moreover, the safe performance of the procedure depends on the simultaneous hand-eye coordination. Nevertheless, despite the euphoria ultrasound technology should only be used in pain management with sufficient indications.

[Neuropathic and tumour-induced headache: Therapeutic options]. / Neuropathischer und tumorbedingter Kopfschmerz : Therapieoptionen.

Cancer pain in the field of otolaryngology can be effectively alleviated. Only very few questions regarding the patient's history of pain are required to understand the type of pain being dealt with and to be able to make the correct selection of analgetic agents. It is particularly important to treat tumor breakthrough pain appropriately, for which a sufficient number of therapeutic agents are available. The present article comments on the various possibilities of specific drugs and interventional therapeutic approaches, as well as their specific characteristics within the field of otolaryngology, supplemented with various tricks for their practical application. Using these basic rules, most problems can be identified and specific treatments optimized. The progression of cancer pain may show wide dynamic ranges, and the therapeutic approach should always be adjusted to the current situation. Palliative care of a cancer patient may be particularly challenging in that, not only the treatment of pain, but also the treatment of respiratory distress is of key importance.

Randomized clinical trial of perianal surgery performed under spinal saddle block versus total intravenous anaesthesia.

BACKGROUND: The aim of this randomized clinical trial was to determine whether spinal saddle block (SSB) is superior to total intravenous anaesthesia (TIVA) in perianal surgery. METHODS: Suitable patients aged 18-75 years (American Society of Anesthesiologists grade I or II) scheduled to undergo perianal surgery were randomized to SSB (1.0 ml 0.5 per cent hyperbaric bupivacaine) or TIVA with propofol and fentanyl by means of a laryngeal mask. Cumulative consumption of analgesics within 24 h after surgery was recorded, and postoperative recovery and patient satisfaction were evaluated. RESULTS: A total of 201 patients were randomized. Supplemental analgesia within 24 h after surgery was required by 31 of 101 patients having SSB and 58 of 100 who had TIVA (P < 0.001). Median monitoring time in the recovery room was 5 (range 1-45) min for SSB versus 44 (4-148) min for TIVA (P < 0.001). Patients in the SSB group were able to eat and drink more quickly, although times to mobilization and micturition were not significantly different. Patients having SSB were more likely to describe the anaesthesia as 'better than expected'. CONCLUSION: SSB is superior to TIVA in patients undergoing perianal surgery in terms of analgesic consumption within 24 h after surgery and aspects of postoperative recovery. REGISTRATION NUMBER: ISRCTN41981381 (http://www.controlled-trials.com).

Injection pain of rocuronium and vecuronium is evoked by direct activation of nociceptive nerve endings.

BACKGROUND AND OBJECTIVE: Rocuronium and, to a lesser extent, vecuronium can induce burning sensations associated with withdrawal reactions during administration. Dermal microdialysis in human and electrophysiological recordings of nociceptors in mouse skin were used to elucidate the underlying mechanisms of pain induction. METHODS: Microdialysis catheters were inserted intradermally into the forearm of 10 volunteers and were perfused with two different concentrations of rocuronium and vecuronium (1 and 10 mg mL(-1)) or a control. Dialysis samples were taken every 15 min and analysed for protein, histamine, tryptase and bradykinin content. Pain intensity was rated on a numerical scale of 0-10. In a parallel design, activation of cutaneous nociceptors was assessed directly in a skin-nerve in vitro preparation of the mouse hind paw. The receptive fields of identified single C-nociceptors (n = 12) were superfused with rocuronium or vecuronium solutions (10 mg mL(-1)) at physiological pH. RESULTS: In accordance with clinical observations, microdialysis of rocuronium (10 mg mL(-1)) induced sharp burning pain (NRS 4.1 +/- 1.8), whereas vecuronium given in the usual clinical concentration (1 mg mL(-1)) induced only minor pain sensations (NRS 0.6 +/- 1.3). At equimolar concentrations, pain sensation and concomitant mediator release evoked by both drugs were similar. No correlations were found between pain rating and mediator release. In the in vitro preparation, C-fibres showed a consistent excitatory response with rapid onset after stimulation with vecuronium as well as rocuronium (differences not significant). CONCLUSIONS: The algogenic effect of aminosteroidal neuromuscular blocking drugs can be attributed to a direct activation of C-nociceptors.

[Screening for neuropsychological deficits--a screening test also for dementias?]. / Neuropsychologisches Defizit-Screening--ein Suchtest auch für Demenzen?

To assess further the psychometric features of neuropsychological deficit screening (NDS), three groups of patients (41 demented, 23 not demented but cognitively impaired, and 50 controls) were examined and the results compared with two older tests, the Mattis dementia rating scale (MDRS) and the mini mental status test (MMST). As a result, the discriminating ability of NDS (modified for this study) was comparable to both other tests without surpassing them in either demented or cognitively impaired groups. An abbreviated version allowed for an improvement in economy without sacrificing discriminating properties. The advantage of NDS thus lies in the diversity of functions assessed, while its screening power is comparable to the two other tests used for comparison.

Different patterns of mast cell activation by muscle relaxants in human skin.

BACKGROUND: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. RESULTS: For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. CONCLUSIONS: Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.

Transesophageal echocardiography and clinical features of fat embolism during cemented total hip arthroplasty. A randomized study in patients with a femoral neck fracture.

Forty patients suffering from a medial femoral neck fracture participated in a prospective, randomized study. In 20 patients, the femoral component was cemented using a contemporary technique. In the patient group operated on with the bone vacuum technique, the medullary cavity was drained during the insertion of the stem. The proximal draining hole was placed in the intertrochanteric region, along the prolongation of the linea aspera. The distal hole was placed 2 cm below the tip of the femoral component. Embolic phenomena were documented intraoperatively by continuous transesophageal echocardiographic imaging of the right atrium and ventricle. The clinical relevance of the emboli was noted simultaneously by recording hemodynamic and blood gas parameters. Patients of the control group showed severer and longer-lasting episodes of embolism than patients of the bone vacuum group. Ongoing emboli were first seen during the injection of the cement, and continued during stem insertion. Massive emboli of small particles could be verified in 19 patients (95%) of the control group and in 1 patient (5%) of the bone vacuum group (P < 0.05). During massive emboli, a distinct decrease in the arterial oxygen saturation and the end-expiratory carbon dioxide level was observed. The calculated average pulmonary shunt volume showed an increase after the insertion of the stem using the contemporary technique (36.5%; P < 0.05). These distinct hemodynamic changes were not observed in the bone vacuum group. This study was able to show a clearly reduced risk of pulmonary emboli using the bone vacuum cementing technique. The presence of pre-existing disease greatly magnified the clinical relevance of fat embolism.

The effects of intradermal fentanyl and ketamine on capsaicin-induced secondary hyperalgesia and flare reaction.

UNLABELLED: In this study, we evaluated the effects of intradermal fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In addition, we obtained dose-response curves for possible local anesthetic effects. Saline (200 microL) and either fentanyl (1 microg or 10 microg in 200 microL) or ketamine (100 microg or 1000 microg in 200 microL) were injected simultaneously into the central volar forearm of 12 healthy volunteers. Nine minutes later, capsaicin (10 microg in 20 microL) was injected intracutaneously exactly between the two injection sites. Areas of touch-evoked allodynia and pinprick hyperalgesia, as well as intensity of pinprick hyperalgesia at the injection sites and axon-reflex flare, were evaluated. Fentanyl did not affect the area or intensity of secondary hyperalgesia. Only the larger concentration of fentanyl locally diminished axon-reflex flare without affecting mechanical detection thresholds. Inhibitory effects of ketamine on intensity of secondary hyperalgesia and axon reflex flare were observed only in the larger concentration. However, this concentration also clearly elevated mechanical detection thresholds. No inhibitory effects of ketamine in the smaller concentrations were observed. We conclude that fentanyl inhibits neuropeptide release on peripheral application without modulating secondary hyperalgesia. Ketamine failed to inhibit both secondary hyperalgesia and axon reflex flare as long as nonlocal anesthetic concentrations were applied. IMPLICATIONS: We investigated the peripheral effects of fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In large concentrations, the opioid diminished axon-reflex flare without effects on secondary hyperalgesia. We found no evidence for the involvement of endogenous glutamate in secondary hyperalgesia or axon reflex flare.

Pain and inflammatory hyperalgesia induced by intradermal injections of human platelets and leukocytes.

Acute and prolonged inflammatory processes, induced by intradermal injections of autologous platelet preparations, leukocytes, platelet-leukocyte mixtures and vehicle solutions, were monitored in 20 human subjects for up to 48 h. Psychophysical methods were employed to assess the time course of pain response, and the development of hyperalgesia. Time course of the axon reflex erythema was analysed by computer based videography. Injections of functionally intact platelets [4.4 x 10(7)+/- 0.6 x 10(7)in 50 µl (mean +/- SEM)] caused distinct pain sensations [median pain rating 7.25 (25-75%: 6.5-7.5) on a scale form 0-10]. Both platelets injected through a microfilter (0.2 µm) and heat-inactivated platelets induced similar initial pain response; however, pain duration was significantly shorter than for intact platelets. Control injections of leukocytes (5.4 x 10(6)+/- 3.7 x 10(6)in 50 µl) and of vehicle solutions only caused minute pain sensations.Although platelet concentration in the mixture was only 50%, platelet/leukocyte mixtures produced axon reflex erythema that were significantly larger than those seen with naive platelets alone (11.1 +/- 2.3 vs 8.3 +/- 0.8 cm(2)). Intact platelets and heat-inactivated platelets both induced mechanical hyperalgesia and skin indurations at the injection site. Both reactions peaked between 6 and 24 h after the injection and disappeared within 48 h. Neither hyperalgesia, nor the development of indurations was noted at the injection sites of filtered platelets and vehicle solutions. Leukocyte injections induced hyperalgesia and indurations only in samples with a platelet contamination of more than 50 000 cells/µl. We conclude that platelets induce acute pain responses due to a soluble factor, whereas the development of hyperalgesia and the formation of indurations depends on a membrane-bound factor. Moreover, platelets and leukocytes act synergistically in nociceptor activation. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Intracutaneous injections of platelets cause acute pain and protracted hyperalgesia.

Suspensions of autologous, washed platelets were intracutaneously injected at the volar forearms of healthy volunteers. Injections of serum and vehicle served as control. Subjects and experimenter were blind with respect to the sequence of injections. In contrast to serum and solvent solution, platelets induced graded burning pain lasting several minutes. Platelet but not serum or vehicle injections dose-dependently caused large axon-reflex flares. At the site of platelet injections an induration developed and in parallel delayed mechanical and heat hyperalgesia was observed. Hyperalgesia to pressure and impact stimulation reached a maximum after 6 h and subsided during the following 48 h. Also, the threshold to heat stimuli decreased moderately by about 1 degree C, on average, after 24 h. Neither indurations nor hyperalgesia could be detected at the injection sites of serum or vehicle. The pathophysiological significance of this new inflammatory model for the research of posttraumatic hyperalgesia is discussed.

Experience with deep hypothermia and elective circulatory arrest for cardiac surgery in infants.

During hypothermic circulatory arrest (19 C nasal) averaging 55 minutes in 25 infants, the mean increase in base deficit was only --3.95 mEq/liter, when arterial gases before circulatory arrest were compared with samples ten minutes after perfusion had been resumed. Few significant arrhythmias occurred, and all survivors appeared neurologically normal at discharge.

Synthesis and antimicrobial activity of azasteroid-type compounds and related systems. Effect of hydrophilic and lipophilic groups on activity.

Pyrazole-, pyrazolone- and isoxazole-containing systems were prepared from 3,4-dihydro-6-(hexyloxy)-1(2H)-naphthalenone, 3,4-dihydro-6-(hexadecyloxy)-1(2H)-naphthalenone,3,4-dihydro-6(2-dimethylaminoethyloxy)-1-(2H)-naphthalenone, 3,4-dihydro-7-hexyloxy-1(2H)-phenanthrone, and 3,4-dihydro-7-(2-dimethylaminoethyloxy)-1(2H)-phenanthrone. A number of compounds derived from 7, 8-dihydro-5(6H)-quinolinone were also synthesized and characterized. Both hydrophilic and lipophilic groups were incorporated into certain systems as well as cidal groups. The compounds were screened for their in vitro inhibitory activity against Bacillus subtilis and Pseudomonas fluorescens. Structure-acitivity relationships among the molecular systems are discussed.