A diagnostic dilemma: distinguishing a sulfasalazine induced DRESS hypersensitivity syndrome from a CD30 + lymphoma in a young patient.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction characterized by cutaneous rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and life-threatening organ dysfunctions. We describe the case of a 26 year old patient admitted to the Emergency Department for DRESS syndrome after sulfasalazine treatment for rheumatoid arthritis in the right knee. Whole body computer tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly, massive ascites and severe hepatic cytolysis. Serology results for Epstein-Barr Virus (EBV), influenza, measles, rubella, hepatitis A and B were negative. The histologic analysis of skin, lymph node and bone marrow biopsies could not indicate a classical Hodgkin's Disease or iatrogenic immunodeficiency/EBV-associated lymphoproliferative disorder (LPD), Hodgkin type. The relatively small caliber of the CD30 + immunoreactive blastoid cells in the lymph nodes suggested reactive immunoblasts rather than Hodgkin cells. The morphologic aspects of the lymph node biopsies with predominance of T-cells were compatible with the diagnosis of a sulfasalazine-induced DRESS syndrome as the patient had a high RegiSCAR score for DRESS. [DRESS Syndrome Foundation: Diagnosis and Treatment. (2023)] The patient's complex clinical course, marked by two hospital admissions, highlights the challenges in diagnosing and managing DRESS. This case underscores the need for individualized care, close patient monitoring, and further research to better understand DRESS's underlying mechanisms and optimal therapeutic strategies.

The relationship between postoperative opioid consumption and the incidence of hypoxemic events following total hip arthroplasty: a post hoc analysis.

Background: Postoperative opioid analgesia may cause respiratory depression. We assessed whether following total hip arthroplasty, placebo-adjusted reductions in morphine consumption at 48 hours with parecoxib (47.0%), propacetamol (35.1%) or parecoxib plus propacetamol (67.9%) translated into a reduction in hypoxemic events. Methods: This was a post hoc analysis of a randomized, placebo-controlled, noninferiority study. Patients were randomly assigned to receive intravenous parecoxib (40 mg twice daily), propacetamol (2 g 4 times daily), parecoxib plus propacetamol (40 mg twice daily + 2 g 4 times daily) or placebo. Dose, date and time of morphine administration via patient-controlled analgesia were monitored throughout the study. In patients not receiving supplemental oxygen, peripheral blood oxygenation was assessed continuously for 48 hours after surgery. Hypoxemia was defined as peripheral oxygen saturation less than 90%. The times and oximeter readings of hypoxemic events were recorded. Pearson correlation coefficient was used to assess for correlations between cumulative morphine consumption at 48 hours and mean number of hypoxemic events. Results: A significantly smaller proportion of patients who received the combined treatment with parecoxib and propacetamol had hypoxemia versus placebo (2.8% v. 13.2%, p < 0.05), and the mean number of hypoxemic events was significantly smaller for parecoxib (0.12), propacetamol (0.06) and parecoxib plus propacetamol (0.03) versus placebo (0.36; all p < 0.05). There was no correlation between the reduction in cumulative morphine consumption at 48 hours and the mean number of hypoxemic events in any treatment group (all p > 0.1). Conclusion: Following total hip arthroplasty, a greater than 70% reduction in morphine consumption may be necessary to translate into a corresponding reduction in hypoxemic events.

Contexte: L'utilisation d'analgésiques opioïdes en période postopératoire peut provoquer une dépression respiratoire. Nous avons voulu déterminer si, après une arthroplastie totale de la hanche, une réduction de la consommation de morphine à 48 heures par l'administration de parécoxib (47,0 %), de propacétamol (35,1 %) ou d'une combinaison des deux (67,9 %) ­ avec ajustement selon un groupe placebo ­ se traduirait par une réduction du nombre d'épisodes d'hypoxémie. Méthodes: Nous avons effectué une analyse post hoc d'une étude randomisée de non-infériorité avec témoins sous placebo. Après une répartition aléatoire, chaque patient a reçu par intraveineuse du parécoxib (40 mg 2 fois par jour), du propacétamol (2 g 4 fois par jour), une combinaison de parécoxib et de propacétamol (40 mg 2 fois par jour + 2 g 4 fois par jour) ou un placebo. Tout au long de l'étude, la dose, la date et le moment de l'administration de morphine contrôlée par le patient ont été notés. Chez les patients qui ne recevaient pas d'oxygène d'appoint, la saturation périphérique en oxygène a été surveillée de manière continue pendant les 48 heures suivant l'opération. L'hypoxémie a été définie comme une saturation inférieure à 90 %. Le moment et les données d'oxymétrie ont été notés pour chaque épisode d'hypoxémie. Le coefficient de corrélation de Pearson a été utilisé pour évaluer la présence de corrélations entre la consommation cumulative de morphine durant les premières 48 heures et le nombre moyen d'épisodes d'hypoxémie. Résultats: Une proportion significativement plus faible de patients ayant reçu le traitement combiné de parécoxib et de propacétamol ont connu des épisodes d'hypoxémie, comparativement aux patients qui avaient reçu le placebo (2,8 % c. 13,2 %, p < 0,05), et le nombre moyen d'épisodes d'hypoxémie était significativement plus faible dans le groupe ayant reçu du parécoxib (0,12), du propacétamol (0,06) ou une combinaison de parécoxib et de propacétamol (0,03), par rapport au groupe placebo (0,36, p < 0,05 pour tous). Aucune corrélation n'a été observée entre la réduction de la quantité totale de morphine consommée à 48 heures et le nombre moyen d'épisodes d'hypoxémie pour tous les groupes (p > 0,1 pour tous). Conclusion: Après une arthroplastie totale de la hanche, une réduction de la consommation de morphine de plus de 70 % pourrait être nécessaire pour obtenir une réduction correspondante du nombre d'épisodes d'hypoxémie.

Cardiovascular safety of the cyclooxygenase-2 selective inhibitors parecoxib and valdecoxib in the postoperative setting: an analysis of integrated data.

BACKGROUND: Studies of parecoxib, the inactive prodrug of the cyclooxygenase-2 selective inhibitor valdecoxib, and valdecoxib for postoperative pain relief in patients undergoing coronary artery bypass graft surgery revealed an increased risk of cardiovascular (CV) adverse events compared with placebo. We conducted this study to address whether parecoxib and valdecoxib increased CV risk in noncardiac surgery patients. METHODS: A pooled post hoc analysis was conducted using 2 large datasets: 17 controlled trials of parecoxib for noncardiac studies and 32 studies, including the 17 noncardiac parecoxib studies plus 15 studies of valdecoxib. The 32-study dataset provided 95% power to detect a twofold increase in the incidence of CV adverse events assuming a placebo group incidence of 1% (estimated from previous study data), and 69% power to detect a twofold increase from a 0.5% incidence. RESULTS: The incidence of total CV events for the 17 parecoxib studies was 0.44% (13 of 2966) in patients who received parecoxib and 0.37% (7 of 1915) in those receiving placebo (P > 0.20). In the analysis of 32 studies, the incidence of total CV events was 0.40% (21 of 5285) in the parecoxib/valdecoxib group compared with 0.50% (16 of 3226) in the placebo group (P > 0.20). No significant differences in the incidence of total or any individual CV event category were observed between the parecoxib or parecoxib/valdecoxib and placebo groups in the two analyses. When patients were stratified by number of baseline CV risk factors, no significant difference in CV events was detected in parecoxib/valdecoxib patients compared with placebo. CONCLUSIONS: In the largest analysis of the CV risk of cyclooxygenase selective inhibitors or nonsteroidal antiinflammatory drugs for perioperative pain management, parecoxib and valdecoxib were not found to increase the risk of CV adverse events after noncardiac surgery.

Is smaller necessarily better? A systematic review comparing the effects of minilaparoscopic and conventional laparoscopic cholecystectomy on patient outcomes.

BACKGROUND: In recent years, minilaparoscopic cholecystectomy (MLC; total size of trocar incision < 25 mm) has been increasingly advocated for the removal of the gallbladder, due to potentially better surgical outcomes (e.g., better cosmetic result, reduced pain, shorter hospital stay, quicker return to activity), but an evidence-based approach has been lacking. The current systematic review was undertaken to evaluate the importance of total size of trocar incision in improving surgical outcomes in adult laparoscopic cholecystectomy (LC). METHODS: The literature was systematically reviewed using MEDLINE and EmBASE. Only randomized controlled trials in English, investigating minilaparoscopic versus conventional LC (total size of trocar incision > or = 25 mm) and reporting pain scores were included. Quantitative analyses (meta-analyses) were performed on postoperative pain scores and other patient outcomes from more than one study where feasible and appropriate. Qualitative analyses consisted of assessing the number of studies showing a significant difference between the techniques. RESULTS: Thirteen trials met the inclusion criteria. There was a trend towards reduced pain with MLC compared with conventional LC, without reduction in opioid use. Patients in the MLC group had slightly reduced length of hospital stay, but there were no significant differences for return to activity. The two interventions were also similar in terms of operating times and adverse events, but MLC was associated with better cosmetic result (largely patient rated). There was a significantly greater likelihood of conversion to conventional LC or to open cholecystectomy in the MLC group than there was of conversion to open cholecystectomy in the conventional LC group [OR 4.71 (95% confidence interval 2.67-8.31), p < 0.00001]. CONCLUSIONS: The data included in this review suggest that reducing the size of trocar incision results in some limited improvements in surgical outcomes after LC. However, it carries a higher risk of conversion to conventional LC or open cholecystectomy.

A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia.

BACKGROUND: Thoracotomy induces severe postoperative pain and impairment of pulmonary function, and therefore regional analgesia has been intensively studied in this procedure. Thoracic epidural analgesia is commonly considered the "gold standard" in this setting; however, evaluation of the evidence is needed to assess the comparative benefits of alternative techniques, guide clinical practice and identify areas requiring further research. METHODS: In this systematic review of randomized trials we evaluated thoracic epidural, paravertebral, intrathecal, intercostal, and interpleural analgesic techniques, compared to each other and to systemic opioid analgesia, in adult thoracotomy. Postoperative pain, analgesic use, and complications were analyzed. RESULTS: Continuous paravertebral block was as effective as thoracic epidural analgesia with local anesthetic (LA) but was associated with a reduced incidence of hypotension. Paravertebral block reduced the incidence of pulmonary complications compared with systemic analgesia, whereas thoracic epidural analgesia did not. Thoracic epidural analgesia was superior to intrathecal and intercostal techniques, although these were superior to systemic analgesia; interpleural analgesia was inadequate. CONCLUSIONS: Either thoracic epidural analgesia with LA plus opioid or continuous paravertebral block with LA can be recommended. Where these techniques are not possible, or are contraindicated, intrathecal opioid or intercostal nerve block are recommended despite insufficient duration of analgesia, which requires the use of supplementary systemic analgesia. Quantitative meta-analyses were limited by heterogeneity in study design, and subject numbers were small. Further well designed studies are required to investigate the optimum components of the epidural solution and to rigorously evaluate the risks/benefits of continuous infusion paravertebral and intercostal techniques compared with thoracic epidural analgesia.

Postpartum seizures after epidural analgesia: a patient with a mutation of the factor V Leiden and prothrombin gene.

We report the case of a 27-year-old parturient who developed a headache within 12 hours of delivery and who subsequently seized. Further examination, including magnetic resonance imaging and computed tomographic scan, showed a partial thrombosis of a transversal venous sinus, the underlying cause being an activated protein C resistance caused by a heterozygote factor V Leiden mutation and heterozygote prothrombin-gene mutation G20210A. Seven months after delivery, the patient is in good health, showing no neurocognitive disability.

PROSPECT: evidence-based, procedure-specific postoperative pain management.

UNLABELLED: Existing general guidelines for perioperative pain management do not consider procedure-specific differences in analgesic efficacy or applicability of a given analgesic technique. For the clinician, an evidence-based, procedure-specific guideline for perioperative pain management is therefore desirable. This chapter reviews the methodology and results of PROSPECT: a public web site (www.postoppain.org) which provides information and recommendations for evidence-based procedure-specific postoperative pain management.

Peripheral inflammation modifies the effect of intrathecal IL-1beta on spinal PGE2 production mainly through cyclooxygenase-2 activity. A spinal microdialysis study in freely moving rats.

Acute inflammation induces upregulation of IL-1beta both at the site of the peripheral inflammation and in the cerebrospinal fluid (CSF). The central increase of IL-1beta mainly contributes to the development of hypersensitivity. However, the spinal mechanisms for the effects of IL-1beta in nociceptive transmission are incompletely understood. It is also unknown whether previous sensitization changes IL-1beta activity. We therefore investigated the dose-effect relationship of intrathecal (i.t.) IL-1beta on spinal PGE(2) production in the absence and presence of peripheral formalin inflammation with spinal microdialysis in freely moving rats. The possible involvement of cyclooxygenase (COX) isoforms in the IL-1beta-mediated spinal PGE(2) production on the background of peripheral formalin inflammation was further evaluated with the selective COX-1 and COX-2 inhibitors. We found that the i.t. administration of IL-1beta, with doses of 1, 2, 8, or 16 ng, increased PGE(2) levels in CSF in a dose-related fashion. This IL-1beta-evoked PGE(2) release occurred within 30min after IL-1beta administration, peaked at 30-60 min interval, and returned gradually to the baseline level within 4h. Peripheral formalin inflammation in the paw induced a more prolonged effect of spinal IL-1beta with larger PGE(2) releases in the CSF compared with the non-inflammatory state, suggesting that peripheral inflammation enhances central sensitization. The COX-2 inhibitor SC58236 (15 mg/kg) reduced the IL-1beta-mediated PGE(2) increase in CSF by 86% while the COX-1 inhibitor SC58560 (15 mg/kg) had less effect (28%). Our study suggests that mainly the COX-2 enzyme mediates the IL-1beta-induced increase in spinal PGE(2) in the presence of peripheral formalin inflammation.

Ropivacaine 3.75 mg/ml, 5 mg/ml, or 7.5 mg/ml for cervical plexus block during carotid endarterectomy.

OBJECTIVE: To examine the effect of 225 mg (7.5 mg/mL), 150 mg (5 mg/mL), and 112.5 mg (3.75 mg/mL) ropivacaine on quality of cervical plexus block during carotid endarterectomy. METHODS: Patients (n = 93) scheduled for carotid endarterectomy were randomized to receive a cervical plexus block with deep infiltration of 10 mL and superficial infiltration of 20-mL volumes of ropivacaine 7.5, 5.0, or 3.75 mg/mL. Pain, coughing, hemodynamic consequences of the block, postoperative visual analog scores, and pain satisfaction index were recorded. If necessary, anesthesia supplements with aliquots of 3 mL lidocaine 1% were given during surgery. RESULTS: Incidences of coughing and hoarseness were similar in all groups. More local anesthetic infiltrations were required in the ropivacaine 3.75-mg/mL and 5-mg/mL groups. Postoperatively, no intragroup differences were observed. A trend toward better pain satisfaction was observed in the ropivacaine 7.5-mg/mL group. CONCLUSION: The best quality of cervical plexus block associated with the smallest incidence of pain for patients undergoing carotid endarterectomy was obtained with 30 mL of 225 mg and 150 mg of ropivacaine, respectively.

Intrathecal catheterization and solvents interfere with cortical somatosensory evoked potentials used in assessing nociception in awake rats.

We assessed the objective measurement of central sensitization processes in the awake rat after subcutaneous formalin with cortical somatosensory evoked potentials (CSEPs). Cranial extradural electrodes and intrathecal catheters were implanted in adult male Wistar rats. After 7 days of recovery, CSEPs were induced by electrical stimuli at the tail and recorded before/after the injection of 50 microL of 2% formalin into the hindpaw of rats for 1 h. The drug and tested vehicles were delivered intrathecally 5 min before the injection of formalin. The peak-to-peak amplitude of the P1-N1 (the early positive-negative sequence pair of CSEPs) and the baseline-to-peak amplitude of the N2 (the late negative component of CSEPs) were analyzed. We found that the amplitudes of both signals increased (154.3% +/- 10.9% and 168.7% +/- 9.8%, respectively) from 10 min after formalin injection to the end of the 60-min test period. Pretreatment with intrathecal ketorolac dose-dependently prevented the increases induced by formalin in both measured variables. Moreover, the increases in P1-N1 and N2 were markedly attenuated either by intrathecal polyethylene-10 tubing or by the solvents used for injection, thus indicating the need for distinguishing an impaired nociceptive signal from antinociception when the effects of drugs are evaluated.

The role of COX-2 inhibitors in pain modulation.

NSAIDs are the analgesics that are most commonly used world-wide. In the past few years, there have been significant advances in explaining the mechanism of action and clinical efficacy of the drugs belonging to this pharmacological family. Recent data relating to the role of cyclo-oxygenase (COX)-2 in the development of neuronal hyperexcitability and pain hypersensitivity have opened new perspectives in our understanding of the therapeutic effects of these drugs in several painful conditions. The main objective of this brief review is to deal with some physiopathological and pharmacological aspects concerning the role of NSAIDs, with special reference to COX-2 inhibitors, in the treatment of pain.

Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty.

Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects. Valdecoxib is a new, highly selective cyclooxygenase (COX)-2-specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain. The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty. This multicenter, multiple-dose, double-blind, parallel-group study compared the opioid-sparing effects, analgesic efficacy, and safety of 20- and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty. Study medication was first administered 1 to 3 hours preoperatively. The total amount of morphine administered, pain intensity, and patient's global evaluation of study medication were assessed over a period of 48 hours. Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40% less morphine than those receiving placebo after hip arthroplasty. Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo. Valdecoxib and placebo were equally well tolerated. Pre- and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone. Thus, valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients.

Pharmacology of systemic analgesics.

Systemic administration of analgesic drugs is still the most widely used method for providing pain relief in acute painful situations. Opioids may be selected on the basis of their physicochemical characteristics and their diffusion index to the brain. But in clinical practice, their very steep concentration-analgesic effect relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in plasma concentrations of opioids may lead to profound fluctuations in analgesic effect when their plasma and effect-site concentrations are near the minimum effective analgesic concentration (MEAC). Combining drugs acting on different mechanisms of nociceptive modulation offers benefits from additive/synergistic effects and will decrease the incidence of their adverse effects. Evidence-based reviews showed that effective pain relief using non-opioid analgesics relied on paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol share the property of morphine sparing in situations of severe (post-operative) pain. CSIs may be beneficial in patients in whom post-operative bleeding is a major surgical risk as the effects of NSAIDs on coagulation may last for days. Finally, low-dose ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.