Paul-Michel Mertes

Anaphylactic and Anaphylactoid Reactions Occurring during Anesthesia in France in 1999–2000

Background Anaphylactic and anaphylactoid reactions occurring during anesthesia remain a major cause of concern for anesthesiologists. The authors report the results of a 2-yr survey of such reactions observed during anesthesia in France. Methods Between January 1, 1999, and December 31, 2000, 789 patients who experienced immune-mediated (anaphylaxis) or nonimmune-mediated (anaphylactoid) reactions were referred to one of the 40 participating centers. Anaphylaxis was diagnosed on the basis of clinical history, skin tests, and/or specific immunoglobulin E assay. Results Anaphylactic and anaphylactoid reactions were diagnosed in 518 cases (66%) and 271 cases (34%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBAs) (n = 306, 58.2%), latex (n = 88, 16.7%), and antibiotics (n = 79, 15.1%). Rocuronium (n = 132, 43.1%) and succinylcholine (n = 69, 22.6%) were the most frequently incriminated NMBAs. Cross-reactivity between NMBAs was observed in 75.1% of cases of anaphylaxis to an NMBA. No difference was observed between anaphylactoid and anaphylactic reactions when the incidences of atopy, asthma, or drug intolerance were compared. However, atopy, asthma, and food allergy were significantly more frequent in the case of latex allergy when compared with NMBA allergy. Clinical manifestations were more severe in anaphylaxis. The positive predictive value of tryptase for the diagnosis of anaphylaxis was 92.6%; the negative predictive value was 54.3%. The diagnostic value of specific NMBA immunoglobulin E assays was confirmed. Conclusions These results further corroborate the need for systematic screening in the case of anaphylactoid reaction during anesthesia and for the constitution of allergoanesthesia centers to provide expert advice to anesthesiologists and allergists.

Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL study ☆

OBJECTIVES Characterize the incidence, clinical and etiologic features and outcomes of advanced congestive heart failure. BACKGROUND This condition is frequent, severe and costly, yet no population-based epidemiological data are available that take into account modern advances in diagnosis and therapy. METHODS The EPICAL (EPidemiologie de l’Insuffisance Cardiaque Avancee en Lorraine) study was based on a comprehensive registration of patients with ACHF (defined as hospital admission for presence of NYHA class III or IV symptoms, radiological and/or clinical signs of pulmonary congestion and/or signs of peripheral edema, left ventricular ejection fraction 60%) in patients aged 20–80 years during year 1994, in the community of the Lorraine region in France (n = 1,592,263). Average follow-up for readmission to hospital and mortality was 18 months (12–24 months). RESULTS From 2,576 registered patients, 499 were enrolled into the study among which, 358 were new presentations. This represents a crude incidence rate of 225 per million. 46.3% had a coronary heart disease. One-year mortality rate was 35.4% and the rate of mortality and/or readmission to hospital was 81%. Patients were admitted to hospital 2.05 times per year (64% of these for worsening heart failure), spending 27.6 days per year in hospital. Twenty received a heart transplant (4%). On discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS Mortality and hospitalization rate of advanced CHF remain very high despite recent therapeutic progress. Major therapeutic and managed-care research is required.

Clinical StudiesIncidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL study☆

OBJECTIVES Characterize the incidence, clinical and etiologic features and outcomes of advanced congestive heart failure. BACKGROUND This condition is frequent, severe and costly, yet no population-based epidemiological data are available that take into account modern advances in diagnosis and therapy. METHODS The EPICAL (EPidemiologie de l’Insuffisance Cardiaque Avancee en Lorraine) study was based on a comprehensive registration of patients with ACHF (defined as hospital admission for presence of NYHA class III or IV symptoms, radiological and/or clinical signs of pulmonary congestion and/or signs of peripheral edema, left ventricular ejection fraction 60%) in patients aged 20–80 years during year 1994, in the community of the Lorraine region in France (n = 1,592,263). Average follow-up for readmission to hospital and mortality was 18 months (12–24 months). RESULTS From 2,576 registered patients, 499 were enrolled into the study among which, 358 were new presentations. This represents a crude incidence rate of 225 per million. 46.3% had a coronary heart disease. One-year mortality rate was 35.4% and the rate of mortality and/or readmission to hospital was 81%. Patients were admitted to hospital 2.05 times per year (64% of these for worsening heart failure), spending 27.6 days per year in hospital. Twenty received a heart transplant (4%). On discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS Mortality and hospitalization rate of advanced CHF remain very high despite recent therapeutic progress. Major therapeutic and managed-care research is required.

Guidelines for management of intra-abdominal infections.

Intra-abdominal infections are one of the most common gastrointestinal emergencies and a leading cause of septic shock. A consensus conference on the management of community-acquired peritonitis was published in 2000. A new consensus as well as new guidelines for less common situations such as peritonitis in paediatrics and healthcare-associated infections had become necessary. The objectives of these Clinical Practice Guidelines (CPGs) were therefore to define the medical and surgical management of community-acquired intra-abdominal infections, define the specificities of intra-abdominal infections in children and describe the management of healthcare-associated infections. The literature review was divided into six main themes: diagnostic approach, infection source control, microbiological data, paediatric specificities, medical treatment of peritonitis, and management of complications. The GRADE(®) methodology was applied to determine the level of evidence and the strength of recommendations. After summarising the work of the experts and application of the GRADE(®) method, 62 recommendations were formally defined by the organisation committee. Recommendations were then submitted to and amended by a review committee. After 2 rounds of Delphi scoring and various amendments, a strong agreement was obtained for 44 (100%) recommendations. The CPGs for peritonitis are therefore based on a consensus between the various disciplines involved in the management of these patients concerning a number of themes such as: diagnostic strategy and the place of imaging; time to management; the place of microbiological specimens; targets of empirical anti-infective therapy; duration of anti-infective therapy. The CPGs also specified the value and the place of certain practices such as: the place of laparoscopy; the indications for image-guided percutaneous drainage; indications for the treatment of enterococci and fungi. The CPGs also confirmed the futility of certain practices such as: the use of diagnostic biomarkers; systematic relaparotomies; prolonged anti-infective therapy, especially in children.

Self-rating of quality of life provides additional prognostic information in heart failure. Insights into the EPICAL study.

The relationship between quality of life (QoL) and survival have been poorly investigated. The aim of this study was to determine the value of QoL score as a prognostic factor in a prospective cohort of patients with advanced chronic heart failure (CHF).

Anaphylaxis to dyes during the perioperative period: Reports of 14 clinical cases

BACKGROUND Vital dyes are widely used for lymphatic mapping and sentinel lymph node biopsy in patients with malignant tumors, and reports of anaphylactic reactions are becoming more frequent. OBJECTIVE Our aims were to describe specific clinical features of hypersensitivity reactions to Patent Blue (Guerbet, Roissy, France), results of the allergy workup, and their consequences for patient management. METHODS We report a series of 14 clinical cases of dye-induced anaphylaxis recorded between 2004 and 2006 in 4 member centers of a network of French allergoanesthesia outpatient clinics. RESULTS Reactions appeared to be relatively severe (6/14 grade III reactions). An average 30 +/- 6-minute delay was observed between dye injection and symptom onset. In 9 (65%) patients reactions were sustained for several hours, requiring prolonged continuous epinephrine infusion and transfer to an intensive care unit. Prick test results were positive in 8 patients. In 5 patients prick test results were negative, whereas intradermal test results were positive. CONCLUSION Anesthesiologists and allergologists must be aware of this specific risk and of the clinical characteristics of these reactions, which are usually delayed and long lasting.

Severe anaphylactic shock with methylene blue instillation.

We report a documented severe immunoglobulin E-mediated hypersensitivity reaction associated with use of 1% methylene blue for detection of tubal permeability occurring during general anesthesia. Clinical symptoms, biological assessment results, and cutaneous test positivity confirmed an anaphylactic reaction to methylene blue. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the perioperative period in the event of a hypersensitivity reaction occurring during anesthesia. Anesthesiologists should be aware of the possibility of hypersensitivity reactions involving any drug or substance used during surgery.

National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study

To cite this article: Johansson SGO, Florvaag E, Öman H, Poulsen LK, Mertes PM, Harper NJN, Garvey LH, Gerth van Wijk R, Metso T, Irgens A, Dybendal T, Halsey J, Seneviratne SL, Guttormsen AB. National pholcodine consumption and prevalence of IgE‐sensitization: a multicentre study. Allergy 2010; 65: 498–502.

Improvement of donor myocardial function after treatment of autonomic storm during brain death.

Background. In experimental brain death models, autonomic storm (AS) triggers severe myocardial dysfunction, which can be attenuated by pharmacologic treatment. The aim of this study was to determine the incidence of AS in a cohort of human organ donors and to evaluate the potential interest of AS treatment on myocardial function, cardiac harvesting and transplantation. Methods. The cohort consisted of 152 patients. Among them, 46 patients were initially considered as potential cardiac donors (main criteria: age <60 years, no history of cardiac disease). AS diagnosis included increased systolic arterial pressure >200 mm Hg associated with tachycardia >140 beats/min. Heart acceptance criteria were associated creatine kinase (CK), troponin Ic, and left ventricle ejection fraction (LVEF) estimated by echocardiography and visual inspection. Results. AS was observed in 29 patients (63%). Hypertension was treated in 12 patients (esmolol n=6, urapidil n=5, nicardipine). Cardiac harvesting was performed in 28 donors (61%). LVEFs were significantly higher after AS treatment (no AS: 55.4±13.4%, untreated AS: 49.0±18.8%, treated AS: 63.9+±10.3%, P=0.049). AS treatment was found to be independently associated with LVEF in >50% of the cases (P=0.034). Treatment of AS or the lack of AS were associated with an increased probability of successful cardiac transplantation (OR=8.8; 95% CI 2.1–38.3, P=0.002). Conclusions. Treatment of hypertension during AS may attenuate brain death-induced myocardial dysfunction and increase the number of available cardiac grafts.

Lipopolysaccharide-Induced Increase of Prostaglandin E2 Is Mediated by Inducible Nitric Oxide Synthase Activation of the Constitutive Cyclooxygenase and Induction of Membrane-Associated Prostaglandin E Synthase

NO produced by the inducible NO synthase (NOS2) and prostanoids generated by the cyclooxygenase (COX) isoforms and terminal prostanoid synthases are major components of the host innate immune and inflammatory response. Evidence exists that pharmacological manipulation of one pathway could result in cross-modulation of the other, but the sense, amplitude, and relevance of these interactions are controversial, especially in vivo. Administration of 6 mg/kg LPS to rats i.p. resulted 6 h later in induction of NOS2 and the membrane-associated PGE synthase (mPGES) expression, and decreased constitutive COX (COX-1) expression. Low level inducible COX (COX-2) mRNA with absent COX-2 protein expression was observed. The NOS2 inhibitor aminoguanidine (50 and 100 mg/kg i.p.) dose dependently decreased both NO and prostanoid production. The LPS-induced increase in PGE2 concentration was mediated by NOS2-derived NO-dependent activation of COX-1 pathway and by induction of mPGES. Despite absent COX-2 protein, SC-236, a putative COX-2-specific inhibitor, decreased mPGES RNA expression and PGE2 concentration. Ketoprofen, a nonspecific COX inhibitor, and SC-236 had no effect on the NOS2 pathway. Our results suggest that in a model of systemic inflammation characterized by the absence of COX-2 protein expression, NOS2-derived NO activates COX-1 pathway, and inhibitors of COX isoforms have no effect on NOS2 or NOS3 (endothelial NOS) pathways. These results could explain, at least in part, the deleterious effects of NOS2 inhibitors in some experimental and clinical settings, and could imply that there is a major conceptual limitation to the use of NOS2 inhibitors during systemic inflammation.