Optimization of cerebral oxygenation based on regional cerebral oxygen saturation monitoring during carotid endarterectomy: A Phase III multicenter, double-blind randomized controlled trial.

BACKGROUND: Whether the optimization of cerebral oxygenation based on regional cerebral oxygen saturation (rSO2) monitoring reduces the occurrence of cerebral ischemic lesions is unknown. METHODS: This multicenter, randomized, controlled trial recruited adults admitted for scheduled carotid endarterectomy. Patients were randomized between the standard of care or optimization of cerebral oxygenation based on rSO2 monitoring using near-infrared spectroscopy. In the intervention group, in case of a decrease in rSO2 in the intervention, the following treatments were sequentially recommended: (1) increasing oxygenotherapy, (2) reducing the tidal volume, (3) legs up-raising, (4) performing a fluid challenge and (5) initiating vasopressor support. The primary endpoint was the number of new cerebral ischemic lesions detected using magnetic resonance imaging pre- and postoperatively. Secondary endpoints included new neurological deficits and mortality on day 120 after surgery. RESULTS: Among the 879 patients who were randomized, 665 (75.7%) were men. There was no statistically significant difference between groups for the mean number of new cerebral ischemic lesions per patient up to 3 days after surgery: 0.35 (±1.05) in the standard group vs. 0.58 (±2.83), in the NIRS group; mean difference, 0.23 [95% CI, -0.06 to 0.52]; estimate, 0.22 [95% CI, -0.06 to 0.50]. New neurological deficits up to day 120 after hospital discharge were not different between the groups: 15 (3,39%) in the standard group vs. 42 (5,49%) in the NIRS group; absolute difference, 2,10 [95% CI, -0,62 to 4,82]. There was no significant difference between groups for the median [IQR] hospital length of stay: 4.0 [4.0 to 6.0] in the standard group vs 5.0 [4.0-6.0] in the NIRS group; mean difference, -0.11 [95% CI, -0.65 to 0.44]. The mortality rate on day 120 was not different between the standard group (0.68%) vs. the NIRS group (0.92%); absolute difference = 0.24% [95% CI, -0.94 to 1.41]. CONCLUSIONS: Among patients undergoing carotid endarterectomy, optimization of cerebral oxygenation based on rSO2 did not reduce the occurrence of cerebral ischemic lesions postoperatively compared with controlled hypertensive therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01415648.

Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).

Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis. METHODS: ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated. RESULTS: Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions. CONCLUSIONS: Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis. CLINICAL TRIAL REGISTRATION: NCT02250729.

Transversus Abdominis Plane Block in the Treatment of Chronic Postsurgical Abdominal Wall Pain Improves Patient Quality of Life: A Retrospective Study and Literature Review.

BACKGROUND: Although poorly studied, chronic postsurgical neuropathic pain (CPNP) represents the second most frequent chronic neuropathic pain etiology, probably affecting 0.5% to 75% of patients with a severe impact on quality of life (QoL). No consensus or treatment algorithm has been elaborated to date, despite a large variety of approaches now available. Transversus abdominis plane (TAP) block has been endorsed as an efficient treatment for acute postoperative pain although its effect on CPNP in terms of intensity and QoL has yet to be considered. OBJECTIVES: The main aim of this study was to evaluate the efficacy of TAP blocks in terms of QoL on patients suffering from abdominal CPNP, including a socio-economic analysis. Results were compared with those published in the recent literature. STUDY DESIGN: Retrospective, monocentric, observational clinical study. SETTING: This single-center retrospective study was conducted at the Chronic Pain Center, Department of Anesthesia, Robert Debré University Hospital, Reims, France. METHODS: From January 2018 through April 2021, all patients suffering from abdominal CPNP treated with a TAP block were enrolled. QoL was assessed using the SF-12 survey. Socio-economic and demographic data were also collected. A literature review was performed using appropriate Medical Subject Headings (MeSH) terms. RESULTS: A TAP block was administered to 44 consecutive patients suffering from CPNP. After a mean follow-up of 11.8 weeks, 86.7% of the patients reported significant effectiveness of the treatment, including an improvement in QoL (P < 0.001), pain scale ratings (P < 0.001) and analgesic requirement (P < 0.001). In term of socio-economic results, one-fifth of the patients returned to work after treatment. The literature review yielded 60 research studies, only 2 of which met our inclusion criteria. These retrospective studies indicated a 76.5% and 81.9% efficacy rate after 12 and 15.5 weeks, respectively. LIMITATIONS: This was a retrospective study with a small sample size. Further investigation should include medical and economic parameters as well as a comparison of TAP block with second-line drug therapies such as transcutaneous neurostimulation, and capsaicin and lidocaine patches. Other anesthetic molecules such as onobotulinumtoxin A (botulinum toxin) combined with steroids should be assessed for these patients. CONCLUSION: The TAP block is easy to learn, easy to reproduce, and easy to administer. After pooling our results with those from the literature, a TAP block is deemed to be effective for the treatment of CPNP with 82.25% effectiveness over a mean time of 13.9 weeks. A TAP block improves long-term QoL, reduces consumption of painkillers and lowers pain scale scores. Thus, it may reduce health care costs. We argue that A TAP block should be considered early, from the onset of the first pain symptoms.

Diagnostic performance of serial serum total tryptase measurement to differentiate positive from negative allergy testing among patients with suspected perioperative hypersensitivity.

BACKGROUND: Serum total tryptase has been shown to increase during acute allergic reactions (acute tryptase, TA ); however, few studies have investigated the values of TA or a combination of TA and baseline tryptase (TB ) to discriminate positive from negative testing in perioperative hypersensitivity reaction (POH) allergy work-up. The aim of this study was to determine the diagnostic performance of TA in order to differentiate positive from negative allergy testing suspected POH and analyse the diagnostic performance of serial tryptase levels using several formulas. METHODS: All patients from the University hospital of Montpellier and Strasbourg, France, who presented with suspected POH and underwent complete drug allergy work-up between March 2011 and December 2019 with available TA and TB were included. Four formulas, including a change in TA  > 11 (F1), or >2 + 1.2 × TB (F2), or >3 + TB (F3), or >120%TB (F4), were applied. RESULTS: One hundred and sixty-two patients were included, and 131 of them (80.8%) had Grade III or IV reactions. Ninety patients had positive allergy testing. The optimal cut-off value of TA to distinguish positive from negative allergy testing patients was 9.8 µg/L with an AUC of 0.817 (95% CI: 0.752-0.882, p < .001). The 93% PPV threshold for TA was 33 µg/L (95.8% specificity). Paired tryptase levels according to formulas F2 and F3 yielded the highest Youden index (0.54 and 0.53, respectively). CONCLUSION: The optimal cut-off point for TA for distinguishing positive from negative allergy testing suspected POH was 9.8 µg/L. TA value of 33 µg/L was required to achieve >90% PPV.

The ROX index as a predictor of standard oxygen therapy outcomes in thoracic trauma.

BACKGROUND: Thoracic trauma is commonplace and accounts for 50-70% of the injuries found in severe trauma. Little information is available in the literature as to timing of endotracheal intubation. The main objective of this study was to assess the accuracy of the ROX index in predicting successful standard oxygen (SO) therapy outcomes, and in pre-empting intubation. METHODS: Patient selection included all thoracic trauma patients treated with standard oxygen who were admitted to a Level I trauma center between January 1, 2013 and April 30, 2020. Successful standard SO outcomes were defined as non-requirement of invasive mechanical ventilation within the 7 first days after thoracic trauma. RESULTS: One hundred seventy one patients were studied, 49 of whom required endotracheal intubation for acute respiratory distress (28.6%). A ROX index score ≤ 12.85 yielded an area under the ROC curve of 0.88 with a 95% CI [0.80-0.94], 81.63sensitivity, 95%CI [0.69-0.91] and 88.52 specificity, 95%CI [0.82-0.94] involving a Youden index of 0.70. Patients with a median ROX index greater than 12.85 within the initial 24 h were less likely to require mechanical ventilation within the initial 7 days of thoracic trauma. CONCLUSION: We have shown that a ROX index greater than 12.85 at 24 h was linked to successful standard oxygen therapy outcomes in critical thoracic trauma patients. It is our belief that an early low ROX index in the initial phase of trauma should heighten vigilance on the part of the attending intensivist, who has a duty to optimize management.

Clinical reasoning in anaphylactic shock: addressing the challenges faced by anaesthesiologists in real time: A clinical review and management algorithms.

Acute hypersensitivity reactions to drugs occur infrequently during anaesthesia and the peri-operative period. When clinical presentation includes the classical triad, erythema, cardiovascular abnormalities and increased airway pressure, the diagnosis is evident and the challenge is to prescribe a therapeutic regimen according to guidelines and to manage refractory signs in a timely manner. In many situations, however, the initial clinical signs are isolated, such as increased airway pressure or arterial hypotension. Rendering a differential diagnosis with causes and mechanisms other than acute hypersensitivity reactions (AHRs) is difficult, delaying treatment with possible worsening of the clinical signs, and even death, in previously healthy individuals. In these difficult diagnostic situations, clinical reasoning is mandatory, and guidelines do not explicitly explain the elements on which clinical reasoning can be built. In this article, based on clinical evidence whenever available, experimental data and pathophysiology, we propose algorithms that have been evaluated by experts. The goal of these algorithms is to provide explicit elements on which the differential diagnosis of AHRs can be made, accelerating the implementation of adequate therapy.

Epidemiology and outcome of patients admitted to intensive care after anaphylaxis in France: a retrospective multicentre study.

BACKGROUND: Few data are available on patients who have experienced anaphylaxis and were admitted to ICUs. The purpose of this observational study was to describe the epidemiology and management of these patients. METHODS: This was a multicentre retrospective study carried out in 23 French ICUs between 2012 and 2017. All patients who suffered anaphylaxis and were transferred to an ICU were included. Data were collected using an electronic database after approval by an ethics committee. RESULTS: A total of 339 patients were included, and 17 (5%) died secondary to anaphylaxis. The main triggers were drugs (77%), contrast media (11%), and food (7%). Epinephrine was administered before ICU admission in 88% of patients with Grade III anaphylaxis and 100% of patients with Grade IV anaphylaxis. Most patients with Grades III and IV anaphylaxes did not receive the recommended dose of i.v. fluid of 30 ml kg-1 within the first 4 h of ICU admission. The time to epinephrine administration was not statistically different between survivors and non-survivors, but non-survivors received a higher dose of epinephrine (median: 5 [3-10] vs 3 [2-7] mg; P<0.0001), which suggests that some forms of anaphylactic shock may be resistant to epinephrine. In multivariate analysis, only lactate concentration at ICU admission was a predictor of death (odds ratio: 1.47 [1.15-1.88]; P=0.002). CONCLUSIONS: Lactate concentration at ICU admission appeared to be the most reliable criterion for assessing prognosis. Epinephrine is widely used during anaphylaxis, but the volume of fluid resuscitation was consistently lower than recommended. CLINICAL TRIAL REGISTRATION: NCT04290507.

Population Pharmacokinetic-Pharmacodynamic Modeling of Ropivacaine in Spinal Anesthesia.

BACKGROUND: Ropivacaine is frequently used in spinal anesthesia but the relationship between plasma concentrations and sensory block level remains unknown. OBJECTIVE: The aim of this study was to assess the relationship between plasma ropivacaine concentrations and effects during spinal anesthesia. METHODS: Sixty patients aged between 18 and 82 years were included in this study after providing written informed consent. Patients were randomly assigned to receive intrathecal administration of ropivacaine 15, 20 or 25 mg. Blood samples were drawn to determine ropivacaine concentrations, and sensory blockade was assessed using pinprick testing. Ropivacaine plasma concentrations and sensory block level were analyzed using a nonlinear mixed-effects modeling approach with Monolix 4.2.2. Uncertainty of parameters was estimated by bootstrapping. RESULTS: Overall, 216 plasma ropivacaine values and 407 sensory block-related data were available for pharmacokinetic-pharmacodynamic (PK-PD) model evaluation. A two-compartment open model connected to a spinal compartment was selected to describe the PKs of ropivacaine. Sensory block modeling was performed using a sigmoid E max model assuming an equilibration delay between the amount in the depot or spinal compartment and at the effect site. Using multiple linear regression analysis, we were able to demonstrate the importance of dose, age and weight as major predictors of sensory block-level kinetics. CONCLUSIONS: This first population PK-PD model for ropivacaine in spinal anesthesia confirms the relationship between plasma ropivacaine concentrations and effect. We also clarify the relationship between the spread of sensory block level and dose, age and, for the first time, weight. STUDY REGISTRATION: This study was approved by the Reims University Hospital Ethics Committee (protocol: PHRC-2005; registered at Agence Nationale de Sécurité du Médicament et des Produits de Santé ANSM: D60890). This was an open, prospective, monocentric study conducted in the University Hospital of Reims (France).

Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats.

PURPOSE: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. AIM OF THE STUDY: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS. MATERIALS AND METHODS: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured. RESULTS: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L-1 vs. vehicle 52 ± 8 hPa.s.L-1; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L-1; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L-1; p = 0.42). CONCLUSIONS: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Ready-to-use pre-filled syringes of atropine for anaesthesia care in French hospitals - a budget impact analysis.

BACKGROUND: Patient safety is improved by the use of labelled, ready-to-use, pre-filled syringes (PFS) when compared to conventional methods of syringe preparation (CMP) of the same product from an ampoule. However, the PFS presentation costs more than the CMP presentation. OBJECTIVE: To estimate the budget impact for French hospitals of switching from atropine in ampoules to atropine PFS for anaesthesia care. METHODS: A model was constructed to simulate the financial consequences of the use of atropine PFS in operating theatres, taking into account wastage and medication errors. The model tested different scenarios and a sensitivity analysis was performed. RESULTS: In a reference scenario, the systematic use of atropine PFS rather than atropine CMP yielded a net one-year budget saving of €5,255,304. Medication errors outweighed other cost factors relating to the use of atropine CMP (€9,425,448). Avoidance of wastage in the case of atropine CMP (prepared and unused) was a major source of savings (€1,167,323). Significant savings were made by means of other scenarios examined. The sensitivity analysis suggests that the results obtained are robust and stable for a range of parameter estimates and assumptions. STUDY LIMITATIONS: The financial model was based on data obtained from the literature and expert opinions. CONCLUSION: The budget impact analysis shows that even though atropine PFS is more expensive than atropine CMP, its use would lead to significant cost savings. Savings would mainly be due to fewer medication errors and their associated consequences and the absence of wastage when atropine syringes are prepared in advance.

Allergy to local anesthetics: Reality or myth?

The incidence of allergic reactions to local anesthetics is low. Most cases involve a psychogenic reaction rather than an allergic reaction. Additives and preservatives added to local anesthetics may cause allergic reactions. Vascular resorption of epinephrine-containing local anesthetics may produce cardiovascular signs similar to an allergic reaction. Diagnosis of allergy to local anesthetics must be established by skin testing and provocative challenge.

Diagnostic procedure after an immediate hypersensitivity reaction in the operating room.

The diagnosis of a perioperative allergic reaction is based on clinical features associated with a suggestive timeline, the exclusion of other diagnoses, elevated concentrations of degranulation markers (histamine, tryptase), and positive allergy assessments (skin tests, specific IgE). After initiating appropriate treatment, the anesthesiologist should take blood samples to measure histamine and tryptase concentrations just after the reaction and repeat them 1-2hours later to validate the diagnosis of immediate hypersensitivity. A delayed measurement of basal tryptase is useful to rule out mastocytosis and to interpret moderate tryptase levels. The anesthesiologist must inform the patient of the reaction to obtain adhesion and consent to subsequent investigations and must record the timing of the reaction and of the blood sampling, the possible causal agents, and the treatment administered. These data must be shared with the laboratory and the allergist. An adverse drug reaction report must be filed. The gold standard for allergy assessment is skin testing. These tests should be done in an appropriate facility, with experienced staff and in compliance with current guidelines. Specific IgE assays and cellular assays can help when clinical features and skin tests are discordant. Provocation tests are sometimes required. After allergy assessment, the safest protocol for subsequent anesthesia is determined in collaboration with the anesthesiologist. The patient must be informed and carry an allergy alert card.

Epinephrine, compared with arginine vasopressin, is associated with similar haemodynamic effects but significantly improved brain oxygenation in the early phase of anaphylactic shock in rats: An experimental study.

BACKGROUND: In contrast to other types of shock, anaphylactic shock decreases cerebral blood flow more than would be expected from severe arterial hypotension, thus potentially affecting survival through brain ischaemia/hypoxia. We hypothesised that epinephrine (EPI) used as a first-line treatment of anaphylactic shock and arginine vasopressin (AVP) proposed in case of EPI refractoriness may have different effects on brain oxygenation. OBJECTIVES: To compare the effect of EPI and AVP on brain oxygenation under similar macro-haemodynamic target values in an anaphylactic shock model. DESIGN: Prospective laboratory study. SETTING: University laboratory. ANIMALS: Male brown Norway rats (n = 27). INTERVENTIONS: Twenty-seven rats were sensitised with ovalbumin (OVA). Twenty rats had anaphylactic shock induced with OVA and were resuscitated with either 0.9% saline (OVA group), EPI (EPI group) or AVP (AVP group). Sensitised control rats received only 0.9% saline and no OVA (CON group). MAIN OUTCOME MEASURES: Mean arterial pressure (MAP), carotid artery blood flow (CaBF), cerebral cortical blood flow (CBF) and hippocampal oxygen partial pressure (PtiO2) were recorded. RESULTS: All rats in the OVA group died within 15 min. EPI and AVP restored comparable levels of MAP, carotid artery blood flow and CBF, and extended survival time. EPI was associated with biologically relevant and significantly (P < 0.05) higher PtiO2 values (nadir values at 20 min: 25.0 ± 2.2 mmHg) compared with the AVP group (14.9 ± 2.0 mmHg). The slopes of the correlations of MAP vs. PtiO2 and CBF were significantly steeper with AVP (more pressure dependence) compared with EPI. By the end of the experiment, hippocampal PtiO2 values between the EPI (24.1 ± 2.1 mmHg) and the AVP (20.8 ± 2.0 mmHg) groups were similar. CONCLUSION: At early, but not at late time points, resuscitation of anaphylactic shock with EPI or AVP to similar MAP and CBF endpoints resulted in hippocampal PtiO2 being significantly higher after EPI. In addition, the PtiO2 after EPI always remained above the threshold for brain hypoxia, whereas PtiO2 after AVP was below the hypoxic threshold most of the time. Because of this early brain hypoxia, AVP may not be the drug of first choice for resuscitation of anaphylactic shock.

Sedative premedication before surgery--A multicentre randomized study versus placebo.

OBJECTIVE: Anxiolytic premedication before non-ambulatory surgery in adult patients may have become of less importance in an era of better preoperative patient information. Moreover, an oral hypnotic given the night before surgery may be as efficient as an anxiolytic for relieving patient anxiety. These two strategies were compared for superiority to a placebo and to each other for non-inferiority. STUDY DESIGN: Double-blind, randomized, multicentre study versus placebo. Eight hospitals in France. June 2011 to February 2013. PATIENTS: Non-ambulatory consecutive surgical patients undergoing general surgery. METHODS AND INTERVENTIONS: Patients received either zopiclone 7.5mg the night before surgery (n=204), or alprazolam 0.5mg the morning of surgery (n=206) and controls received placebo (n=68). Demographic data, preoperative anxiety, fear of surgery and anaesthesia, and mood were assessed the day before surgery using a visual analogue scale, the Spielberger scale and the APAIS scale. In the operating room, anxiety and comfort were assessed in addition to physiological data. RESULTS: Preoperative data did not differ between groups. In the operating room, anxiety and comfort were moderate and did not differ significantly between groups on a 1-10 scale (median [25-75 percentile]): zopiclone: 2 [1-4] and 2.5 [1-5]; alprazolam: 2 [1,4] and 2 [1-5]; placebo: 3 [1-5] and 3 [1-5]. The patients who were more anxious preoperatively remained so in the operating room, irrespective of the treatment received (r=0.31, p<0.001). A placebo effect was observed in 38% of patients in the corresponding group. Patients receiving zopiclone reported a significantly better sleep the night before surgery compared to other groups (median: 2 vs. 1, p<0.001). CONCLUSIONS: Premedication in non-ambulatory surgery is no more effective than a placebo, owing to the very moderate level of anxiety experienced by patients.

Diagnostic value of histamine and tryptase concentrations in severe anaphylaxis with shock or cardiac arrest during anesthesia.

BACKGROUND: The diagnosis of acute life-threatening allergic reactions during anesthesia relies on clinical signs, histamine and/or tryptase measurements, and allergic testing. In patients who die after the reaction, skin tests cannot be performed, and the effect of resuscitation manoeuvres on mediator concentrations is unknown. The authors compared plasma histamine and tryptase concentrations in patients with severe allergic reactions during anesthesia with those measured in patients with shock due to other causes. METHODS: Patients with life-threatening allergic reactions were retrieved from a previous database (Group ALLERGY). All had positive allergy tests to administered agents. Patients with severe septic/cardiogenic shock or cardiac arrest (Group CONTROL) had histamine and tryptase measurements during resuscitation manoeuvres. Receiver operating characteristics curves were built to calculate the optimal mediator thresholds differentiating allergic reactions from others. RESULTS: One hundred patients were included, 75 in Group ALLERGY (cardiovascular collapse, 67; cardiac arrest, 8) and 25 in Group CONTROL (shock, 11; cardiac arrest, 14). Mean histamine and tryptase concentrations remained unchanged throughout resuscitation in Group CONTROL and were significantly higher in Group ALLERGY. The optimal thresholds indicating an allergic mechanism were determined as 6.35 nmol/l for histamine (sensitivity: 90.7% [95% CI, 81.7 to 96.1]; specificity: 91.7% [73.0 to 98.9]) and 7.35 µg/l for tryptase (sensitivity: 92% [83.4 to 97.0]; specificity: 92% [73.9 to 99.0]). CONCLUSIONS: Resuscitation manoeuvres by themselves did not modify mediator concentrations. Virtually all life-threatening reactions during anesthesia associated with mediator concentrations exceeding the thresholds were allergic events. These findings have potential forensic interest when a patient dies during anesthesia.

[Anaesthetic management of patient with neurological disease: Focus on regional anaesthesia]. / Spécificités de la prise en charge anesthésique chez les patients souffrant de maladie neurologique : éclairage sur l'anesthésie locorégionale.

Anaesthesia of patients with neurological disease is feasible but each specific disease requires specific adjustments accordingly. A preoperative evaluation of neurological status is required and patients should be informed of the potential harms in the perioperative period. Regional anaesthesia is commonly considered as contraindicated in these patients although it is commonly not. General anaesthesia has not been demonstrated to worsen cognitive dysfunction in patients suffering from Alzheimer's disease but these dysfunctions may disturb postoperative rehabilitation. Regional anaesthesia has no special benefit in these patients. In patients with Parkinson's disease, inability to use the oral route in the postoperative period may impair the administration of the treatment. Multiple sclerosis is not a contraindication of epidural anaesthesia especially in obstetrics, since there is no evidence that it may trigger relapse of the disease especially in the postpartum period. Regional anaesthesia is doable in patients with a dysimmune demyelinated lesions out of the regeneration phase of the disease. In peripheral hereditary or acquired neuropathies regional anaesthesia is also feasible. Epilepsy, spina bifida and traumatic pathologies of the spine are not contraindications to regional anaesthesia but the latter require technical adjustment.

Population pharmacokinetics of nefopam in elderly, with or without renal impairment, and its link to treatment response.

AIMS: Nefopam is a nonmorphinic central analgesic, for which no recommendation exists concerning adaptation of regimen in aged patients with or without renal impairment. The objective was to describe the pharmacology of nefopam in aged patients to obtain guidelines for practical use. METHODS: Elderly patients (n = 48), 65-99 years old, with severe or moderate renal impairment or with normal renal function, were recruited. Nefopam (20 mg) was administered as a 30 min infusion postoperatively. Simultaneously, a 1 min intravenous infusion of iohexol was performed, in order to calculate the glomerular filtration rate. Blood samples were drawn to determine nefopam, desmethyl-nefopam and iohexol plasma concentrations. Nefopam and desmethyl-nefopam concentrations were analysed using a nonlinear mixed-effects modelling approach with Monolix version 4.1.3. The association between pharmacokinetic parameters and treatment response was assessed using logistic regression. RESULTS: A two-compartment open model was selected to describe the pharmacokinetics of nefopam. The typical population estimates (between-subject variability) for clearance, volume of distribution, intercompartmental clearance and peripheral volume were, respectively, 17.3 l h(-1) (53.2%), 114 l (121%), 80.7 l h(-1) (79%) and 208 l (63.6%). Morphine requirement was related to exposure of nefopam. Tachycardia and postoperative nausea and vomiting were best associated with maximal concentration and the rate of increase in nefopam plasma concentration. CONCLUSIONS: We identified the nefopam pharmacokinetic predictors for morphine requirement and side-effects, such as tachycardia and postoperative nausea and vomiting. In order to maintain morphine sparing and decrease side-effects following a single dose of nefopam (20 mg), simulations suggest an infusion time of >45 min in elderly patients with or without renal impairment.