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Streptococcal toxic shock syndrome is a severe, invasive and life-threatening infection associated with a high risk of rapid multiorgan failure. It is associated with high morbidity and mortality. Streptococcal toxic shock syndrome is very commonly caused by group A-Streptococcus pyogenes, ß-haemolytic streptococcus, a typical human-specific gram-positive bacterial pathogen. We present here the case report of a 54-year-old man with a rapidly progressive streptococcal toxic shock syndrome due to necrotising fasciitis of the left lower limb and describe the successful treatment through close interdisciplinary care.
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During the COVID 19 pandemic, advanced age, scoring systems, and a shortage of ICU beds were used as cut-offs for ICU admission. This case report describes the epicrisis of an elderly patient who was almost mistakenly not treated in an ICU.
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The long-term stability of drugs under normal laboratory storage conditions (-20°C) for years is important for research purposes, clinical re-evaluation, and also for forensic toxicology. To evaluate the stability of the analgesic opioid hydromorphone, 44 human frozen plasma samples of a former clinical trial were reanalyzed after at least three years. Blood samples were disposed using solid-phase extraction with an additional substitution of stable isotope labelled hydromorphone as an internal standard. Hydromorphone concentrations were determined by ultra-performance liquid chromatography (UPLC) with gradient elution, followed by tandem mass spectrometry with electrospray ionization. Calibration curves demonstrated linearity of the assay in the concentration range of 0.3-20 ng/mL hydromorphone. The limit of detection of the hydromorphone plasma concentration was 0.001 ng/mL, and the lower limit of quantification was 0.3 ng/mL. Intra- and interassay errors did not exceed 16%. The percentage deviation of the measured hydromorphone plasma concentrations between the reanalysis and the first analysis was -1.07% ± 14.8% (mean ± SD). These results demonstrate that hydromorphone concentration in human plasma was stable when the samples were frozen at -20°C over three years. This finding is of value for re-evaluations or delayed analyses for research purposes and in pharmacokinetic studies, such as in forensic medicine.
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BACKGROUND: Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. METHODS: 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. RESULTS: Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. CONCLUSIONS: Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. TRIAL REGISTRATION: Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 .
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COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , COVID-19/terapia , Humanos , Unidades de Cuidados Intensivos , Pandemias , Síndrome de Dificultad Respiratoria/terapia , Análisis de SupervivenciaRESUMEN
OBJECTIVES: To compare the efficacy, safety, and side effects of hydromorphone and morphine administered as patient-controlled analgesia (PCA) for postoperative pain therapy after cardiac surgery with median sternotomy. DESIGN: A retrospective analysis of data from 2 prospective, single-blinded, randomized trials. SETTING: A single-center intensive care unit at a university hospital. PARTICIPANTS: Forty-one adult patients undergoing cardiac surgery with median sternotomy. INTERVENTIONS: Postoperative pain therapy at the intensive care unit was performed by PCA with intravenously administered bolus doses of 0.2 mg of hydromorphone (n = 21) or 2 mg of morphine (n = 20). MEASUREMENTS AND MAIN RESULTS: Pain at rest and under deep inspiration regularly was assessed using the 11-point numerical rating scale (NRS). Blood pressure, heart rate, cardiac output, oxygen saturation, and respiratory rate were monitored, and adverse events were registered. The median (range) NRS rating at rest was 1.5 (0-5) after hydromorphone and 0.5 (0-5) after morphine, respectively (p = 0.41). The median NRS rating under deep inspiration was 3 (0-6) after hydromorphone and 4 (0-7) after morphine, respectively (p = 0.074). The dose ratio of morphine to hydromorphone during PCA was 5.7 (95% confidence interval: 2.9-7.6). Hemodynamics and respiration were stable and did not differ significantly. Postoperative nausea and vomiting were the most frequent adverse events, which were observed in 29% of the patients after hydromorphone and in 35% after morphine, respectively (p = 0.74). CONCLUSIONS: There were no significant differences in analgesic efficacy and safety between hydromorphone and morphine when used for postoperative pain therapy with PCA after cardiac surgery with median sternotomy.
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Procedimientos Quirúrgicos Cardíacos , Hidromorfona , Adulto , Analgesia Controlada por el Paciente , Analgésicos Opioides , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Método Doble Ciego , Humanos , Hidromorfona/efectos adversos , Morfina , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios Prospectivos , Estudios Retrospectivos , Esternotomía/efectos adversosRESUMEN
BACKGROUND: Remifentanil is an effective drug in peri-operative pain therapy, but it can also induce and aggravate hyperalgesia. Supplemental administration of N2O may help to reduce remifentanil-induced hyperalgesia. OBJECTIVE: To evaluate the effect of 35 and 50% N2O on hyperalgesia and pain after remifentanil infusion. DESIGN: Single site, phase 1, double-blind, placebo-controlled, randomised crossover study. SETTING: University Hospital, Germany from January 2012 to April 2012. PARTICIPANTS: Twenty-one healthy male volunteers. INTERVENTIONS: Transcutaneous electrical stimulation induced spontaneous acute pain and stable areas of hyperalgesia. Each volunteer underwent the following four sessions in a randomised order: 50 to 50% N2-O2 and intravenous (i.v.) 0.9% saline infusion (placebo); 50 to 50% N2-O2 and i.v. remifentanil infusion at 0.1 µg kg-1 min-1 (remifentanil); 35 to 15 to 50% N2O-N2-O2 and i.v. remifentanil infusion at 0.1 µg kg-1 min-1 (tested drug) and 50 to 50% N2O-O2 and i.v. remifentanil infusion at 0.1 µg kg-1 min-1 (gas active control). Gas mixtures were inhaled for 60âmin; i.v. drugs were administered for 30 min. MAIN OUTCOME MEASURES: Areas of pin-prick hyperalgesia, areas of touch-evoked allodynia and pain intensity on a visual analogue scale were assessed repeatedly for 160âmin. RESULTS: Data from 20 volunteers were analysed. There were significant treatment and treatment-by-time effects regarding areas of hyperalgesia (Pâ<â0.001). After the treatment period, the area of hyperalgesia was significantly reduced (Pâ<â0.001) in the tested drug and in the gas active control (30.6â±â9.25 and 24.4â±â7.3âcm2, respectively) compared with remifentanil (51.0â±â17.0âcm2). There was also a significant difference between the gas active control and the tested drug sessions (Pâ<â0.001). For the area of allodynia and pain rating, results were consistent with the results for hyperalgesia. CONCLUSIONS: Administration of 35% N2O significantly reduced hyperalgesia, allodynia and pain intensity induced after remifentanil. It might therefore be suitable in peri-operative pain relief characterised by hyperalgesia and allodynia, such as postoperative pain, and may help to reduce opioid demand. TRIAL REGISTRATION: EudraCT-No.: 2011-000966-37.
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Óxido Nitroso , Piperidinas , Analgésicos Opioides , Método Doble Ciego , Voluntarios Sanos , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/diagnóstico , Hiperalgesia/tratamiento farmacológico , Masculino , Dolor Postoperatorio , Piperidinas/efectos adversos , RemifentaniloRESUMEN
BACKGROUND: The challenge of managing acute postoperative pain is the well tolerated and effective administration of analgesics with a minimum of side effects. The standard therapeutic approach is patient-controlled analgesia (PCA) with systemic opioids. To overcome problems of oscillating opioid concentrations, we studied patient-controlled analgesia by target-controlled infusion (TCI-PCA) as an alternative. OBJECTIVE: To compare efficacy, safety and side effects of standard PCA with TCI-PCA for postoperative pain therapy with hydromorphone. DESIGN: Single-blinded, randomised trial. SETTING: University Hospital, Germany from December 2013 to April 2015. PARTICIPANTS: Fifty adults undergoing cardiac surgery. INTERVENTIONS: Postoperative pain therapy on the ICU was managed with intravenous (i.v.) hydromorphone and patients randomised to TCI-PCA with target plasma concentrations between 0.8 and 10ângâml, or PCA with bolus doses of 0.2âmg. Pain was regularly assessed using the 11-point numerical rating scale (NRS). Blood pressure, heart rate, oxygen saturation and cardiac output were continuously monitored, and adverse events were registered throughout the study. MAIN OUTCOME MEASURES: NRS pain ratings, hydromorphone doses, haemodynamic effects and side effects. RESULTS: NRS pain ratings, total doses of hydromorphone and haemodynamic data did not differ significantly between TCI-PCA and PCA. The number of bolus doses during PCA was significantly higher than the number of target increases during TCI-PCA (Pâ=â0.006). The number of negative requests was also significantly higher during PCA than during TCI-PCA (Pâ=â0.02). The respiratory rate on the first postoperative morning was 25â±â6âmin during TCI-PCA, compared with 19â±â4âmin during PCA (Pâ=â0.022). Nausea occurred in 30% after TCI-PCA and 24% after PCA (Pâ=â0.46). CONCLUSION: TCI-PCA was effective and well tolerated in acute postoperative pain management after cardiac surgery. Further studies are needed to evaluate this approach in clinical practice. TRIAL REGISTRATION: EudraCT Number: 2013-002875-16, and ClinicalTrials.gov Identifier: NCT02035709.
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Analgesia Controlada por el Paciente , Hidromorfona , Adulto , Analgésicos Opioides/efectos adversos , Alemania , Humanos , Hidromorfona/efectos adversos , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Estándares de ReferenciaRESUMEN
BACKGROUND: Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. METHODS: Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry. PATIENT FINDINGS: Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage. INTERPRETATION: These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage. FUNDING: Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.
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Infecciones por Coronavirus/patología , Trampas Extracelulares/metabolismo , Microvasos/patología , Neutrófilos/metabolismo , Neumonía Viral/patología , Trombosis/metabolismo , COVID-19 , Células Cultivadas , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Humanos , Microvasos/metabolismo , Neutrófilos/patología , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/metabolismo , Trombosis/etiología , Trombosis/patologíaRESUMEN
BACKGROUND: The effects of environmental changes on the somato-sensory system during long-distance air ambulance flights need to be further investigated. Changes in nociceptive capacity are conceivable in light of previous studies performed under related environmental settings. We used standardized somato-sensory testing to investigate nociception in healthy volunteers during air-ambulance flights. METHODS: Twenty-five healthy individuals were submitted to a test compilation analogous to the quantitative sensory testing battery-performed during actual air-ambulance flights. Measurements were paired around the major changes of external factors during take-off/climb and descent/landing. Bland-Altman-Plots were calculated to identify possible systemic effects. RESULTS: Bland-Altman-analyses suggest that the thresholds of stimulus detection and pain as well as above-threshold pain along critical waypoints of travel are not subject to systemic effects but instead demonstrate random variations. CONCLUSIONS: We provide a novel description of a real-life experimental setup and demonstrate the general feasibility of performing somato-sensory testing during ambulance flights. No systematic effects on the nociception of healthy individuals were apparent from our data. Our findings open up the possibility of future investigations into potential effects of ambulance flights on patients suffering acute or chronic pain.
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Ambulancias Aéreas , Nocicepción , Dolor Nociceptivo/etiología , Enfermedad Relacionada con los Viajes , Adulto , Viaje en Avión , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Umbral del DolorRESUMEN
OBJECTIVE: Evaluate the accuracy and trending ability of the fourth-generation FloTrac/EV1000 (Edwards Lifesciences, Irvine, CA) system in patients with severe aortic valve stenosis by comparing FloTrac/EV1000-derived cardiac output (CCO-FT) with continuous thermodilution pulmonary artery catheter (CCO-PAC) measurements before and after surgical valve replacement. DESIGN: Prospective clinical study. SETTING: Anesthesia for cardiac surgery, operating room, single-center university hospital. PARTICIPANTS: Twenty-five patients were included. After exclusion, 20 patients undergoing elective aortic valve replacement were analyzed. INTERVENTIONS: After induction of general anesthesia, CCO-FT and CCO-PAC values were recorded every 30 seconds before and after aortic valve replacement with a bioprosthesis under cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: Data were analyzed separately from skin incision to last suture and before and after CPB. Regression analyses, Bland-Altman analyses, and trending analyses (4-quadrant plot, polar plot) were performed. The percentage errors of the FloTrac/EV1000 were 69.7% and 59.3% before and after CPB, respectively. The concordance rates (CRs) and angular CRs of the FloTrac/EV1000 were 50.9% and 57.1%, and 48.7% and 61.9% before and after CPB, respectively. CONCLUSION: This study revealed a low level of agreement and poor trending ability of the FloTrac/EV1000 system compared to continuous thermodilution pulmonary artery catheter in patients with severe aortic stenosis. Although there was a slight improvement after surgical valve replacement and CPB, the results were not within acceptable limits to replace CCO-PAC in this patient population.
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Estenosis de la Válvula Aórtica/cirugía , Gasto Cardíaco/fisiología , Cateterismo de Swan-Ganz/tendencias , Implantación de Prótesis de Válvulas Cardíacas/tendencias , Índice de Severidad de la Enfermedad , Termodilución/tendencias , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Cateterismo de Swan-Ganz/normas , Femenino , Implantación de Prótesis de Válvulas Cardíacas/normas , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Termodilución/normasRESUMEN
For the quantification of propofol total and unbound drug concentrations a sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. To separate unbound propofol an ultrafiltration step before sample preparation was performed. Both the ultrafiltrate and plasma samples were extracted with solid-phase extraction and substituted with deuterated propofol as an internal standard. Separation was performed by gradient elution using UPLC-like system and analyzed by MS/MS consisting of an electrospray ionization source. To detect low and high concentration levels of propofol two calibration curves were identified and showed linearity within the range of 1-50ng/ml and 50-20000ng/ml. The lower limit of quantification was 1ng/ml. Intra- and interassay precision and accuracy did not exceed ±15%. The method was applied to a clinical study during intensive care treatment of patients after coronary artery bypass grafting.
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Cromatografía Liquida/métodos , Hipnóticos y Sedantes/farmacocinética , Propofol/farmacocinética , Espectrometría de Masas en Tándem/métodos , Calibración , Cromatografía Líquida de Alta Presión/métodos , Puente de Arteria Coronaria/métodos , Cuidados Críticos , Humanos , Hipnóticos y Sedantes/análisis , Límite de Detección , Propofol/análisis , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Extracción en Fase Sólida/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos , Ultrafiltración/métodosRESUMEN
Topical application of lidocaine is an effective approach for treatment of post-herpetic neuralgia and other painful neuropathies. Lidocaine inhibits voltage-gated Na(+) channels and it most likely reduces excitability of cutaneous sensory neurons which can be hyperexcitable or spontaneously active in states of neuropathic pain. However, lidocaine and other local anesthetics also exert a pronounced neurotoxicity and they activate the irritant receptors TRPV1 and TRPA1. In this randomized and double-blinded study, we explored the ability of lidocaine patches (5%) to alter sensory function and epidermal nerve fiber density in skin of healthy volunteers. As assessed by quantitative sensory testing, significantly elevated thresholds for touch, pin prick pain and mechanically induced wind-up were observed in skin treated with lidocaine patches. These effects reversed to baseline values within 2days after termination of the treatment. Pressure pain and thresholds for heat and cold-induced pain were not affected by the lidocaine patch. A moderate but significant decrease in epidermal nerve fiber density was observed in skin blister roofs obtained after 42days of treatment with lidocaine patches. The placebo patch did not induce any changes in sensory thresholds or nerve fiber density. In conclusion, lidocaine patches seem to have differential effects on sensory modalities in healthy skin. A degeneration of epidermal nerve fibers has previously been demonstrated for patches containing the TRPV1-agonist capsaicin and our findings suggest that this effect might also be relevant for lidocaine patches. These data warrant further studies on molecular mechanisms mediating a relief of neuropathic pain by topical lidocaine.
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Anestésicos Locales/farmacología , Epidermis/efectos de los fármacos , Lidocaína/farmacología , Fibras Nerviosas/efectos de los fármacos , Percepción del Dolor/efectos de los fármacos , Percepción del Tacto/efectos de los fármacos , Administración Cutánea , Adolescente , Adulto , Anestésicos Locales/administración & dosificación , Método Doble Ciego , Epidermis/inervación , Humanos , Lidocaína/administración & dosificación , Masculino , Persona de Mediana Edad , Dimensión del Dolor/efectos de los fármacos , Umbral Sensorial/efectos de los fármacos , Parche TransdérmicoRESUMEN
Crohn's disease (CD) is a painful inflammatory bowel disease with complex multigenic inheritance. Suggested on the basis of a few isolated reports CD patients require significantly higher post operative opioid doses than patients undergoing comparable severe abdominal surgery. Crohn's disease therefore may be a suitable model for the identification of novel pain susceptibility genes. In order to confirm this observation and to elucidate the underlying molecular mechanisms, we investigated if higher opioid needs of CD patients are due to a general change in pain sensitivity. Quantitative sensory testing (QST) was applied to a subgroup of patients and polymorphisms in the mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) were investigated. Significantly increased post operative opioid requirements in CD patients were confirmed and QST assessment demonstrates that CD patients do not display increased pain sensitivity in terms of lowered thresholds to thermal and mechanical stimuli. The data also suggest that common variants in OPRM1 and specific 'high pain sensitivity'COMT haplotypes may not be the cause of high opioid needs. The results indicate that a more complex pathway is involved in the greater post operative opioid demand in CD. Therefore the presence of other, as yet unknown, genes could modulate opioid requirements in CD patients.
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Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Enfermedad de Crohn/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Analgesia Controlada por el Paciente , Catecol O-Metiltransferasa/genética , ADN/genética , ADN/aislamiento & purificación , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Proteína Adaptadora de Señalización NOD2 , Dimensión del Dolor , Dolor Postoperatorio/psicología , Estudios Prospectivos , Receptores Opioides mu/genética , Estudios RetrospectivosRESUMEN
Different mechanisms were proposed for opioid-induced analgesia and antihyperalgesia, which might result in different pharmacodynamics. To address this issue, the time course of analgesic and antihyperalgesic effects of intravenous (i.v.) and sublingual (s.l.) buprenorphine was assessed in an experimental human pain model. Fifteen volunteers were enrolled in this randomized, double-blind, and placebo controlled cross-over study. The magnitude of pain and the area of secondary hyperalgesia following transcutaneous stimulation were repetitively assessed before and up to 150 min after administration of (1) 0.15 mg buprenorphine i.v. and placebo pill s.l., (2) 0.2 mg buprenorphine s.l. and saline 0.9% i.v. or (3) saline 0.9% i.v. and placebo pill s.l. as a control. The sessions were separated by 2 week wash-out periods. For both applications of buprenorphine the antihyperalgesic effects were more pronounced as compared to the analgesic effects (66+/-9 vs. 26+/-5% and 43+/-10 vs. 10+/-6%, for i.v. and s.l. application, respectively). This contrasts the pattern for the intravenous administration of pure mu-receptor agonists in the same model in which the antihyperalgesic effects are weaker. The apparent bioavailability of buprenorphine s.l. as compared to buprenorphine i.v. was 58% with a 15.8 min later onset of antinociceptive effects. The half-life of buprenorphine-induced analgesic and antihyperalgesic effects were 171 and 288 min, respectively. In contrast to pure mu-receptor agonists, buprenorphine exerts a lasting antihyperalgesic effect in our model. It will be of major clinical interest whether this difference will translate into improved treatment of pain states dominated by central sensitization.
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Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Buprenorfina/efectos adversos , Buprenorfina/uso terapéutico , Hiperalgesia/prevención & control , Dolor/tratamiento farmacológico , Administración Sublingual , Adulto , Algoritmos , Analgésicos Opioides/farmacología , Disponibilidad Biológica , Buprenorfina/farmacología , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/diagnóstico , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Dolor/diagnóstico , Dolor/fisiopatología , Dimensión del Dolor/estadística & datos numéricos , Placebos , Receptores Opioides mu/agonistas , Receptores Opioides mu/efectos de los fármacos , Estimulación Eléctrica Transcutánea del Nervio/métodos , Resultado del TratamientoRESUMEN
Non-steroidal antiinflammatory drugs (NSAIDs) are known to induce analgesia mainly via inhibition of cyclooxygenase (COX). Although the inhibition of COX in the periphery is commonly accepted as the primary mechanism, experimental and clinical data suggest a potential role for spinal COX-inhibition to produce antinociception and reduce hypersensitivity. We used an experimental model of electrically evoked pain and hyperalgesia in human skin to determine the time course of central analgesic and antihyperalgesic effects of intravenous parecoxib and paracetamol (acetaminophen). Fourteen subjects were enrolled in this randomized, double blind, and placebo controlled cross-over study. In three sessions, separated by 2-week wash-out periods, the subjects received intravenous infusions of 40 mg parecoxib, 1000 mg paracetamol, or placebo. The magnitude of pain and areas of pinprick-hyperalgesia and touch evoked allodynia were repeatedly assessed before, and for 150 min after the infusion. While pain ratings were not affected, parecoxib as well as paracetamol significantly reduced the areas of secondary hyperalgesia to pinprick and touch. In conclusion, our results provide clear experimental evidence for the existence of central antihyperalgesia induced by intravenous infusion of two COX inhibitors, parecoxib and paracetamol. Since the electrical current directly stimulated the axons, peripheral effects of the COX inhibitors on nociceptive nerve endings cannot account for the reduction of hyperalgesia. Thus, besides its well-known effects on inflamed peripheral tissues, inhibition of central COX provides an important mechanism of NSAID-mediated antihyperalgesia in humans.