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International audience; BackgroundThe optimal dose of tranexamic acid to inhibit hyperfibrinolysis in postpartum haemorrhage is unclear. Tranexamic Acid to Reduce Blood Loss in Hemorrhagic Cesarean Delivery (TRACES) was a double-blind, placebo-controlled, randomised, multicentre dose-ranging study to determine the dose–effect relationship for two regimens of intravenous tranexamic acid vs placebo.MethodsWomen experiencing postpartum haemorrhage during Caesarean delivery were randomised to receive placebo (n=60), tranexamic acid 0.5 g (n=57), or tranexamic acid 1 g i.v. (n=58). Biomarkers of fibrinolytic activation were assayed at five time points, with inhibition of hyperfibrinolysis defined as reductions in the increase over baseline in D-dimer and plasmin–antiplasmin levels and in the plasmin peak time.ResultsIn the placebo group, hyperfibrinolysis was evidenced by a mean increase over baseline [95% confidence interval] of 93% [68–118] for D-dimer level at 120 min and 56% [25–87] for the plasmin–antiplasmin level at 30 min. A dose of tranexamic acid 1 g was associated with smaller increases over baseline (D-dimers: 38% [13–63] [P=0.003 vs placebo]; plasmin–antiplasmin: –2% [–32 to 28] [P=0.009 vs placebo]). A dose of tranexamic acid 0.5 g was less potent, with non-significant reductions (D-dimers: 58% [32–84] [P=0.06 vs placebo]; plasmin–antiplasmin: 13% [18–43] [P=0.051]). Although both tranexamic acid doses reduced the plasmin peak, reduction in plasmin peak time was significant only for the 1 g dose of tranexamic acid.ConclusionsFibrinolytic activation was significantly inhibited by a dose of intravenous tranexamic acid 1 g but not 0.5 g. Pharmacokinetic–pharmacodynamic modelling of these data might identify the best pharmacodynamic monitoring criteria and the optimal tranexamic acid dosing regimen for treatment of postpartum haemorrhage.

Background Pregnant women are at increased risk of hypoxaemia during general anaesthesia. Our aim was to determine the incidence and the risk factors that contribute to hypoxaemia in this setting. Methods Every woman 18 yr or older who underwent a non-elective Caesarean section under general anaesthesia was eligible to participate in this multicentre observational study. The primary endpoint was the incidence of hypoxaemia defined as the SpO2 ≤95%. The secondary endpoint was the incidence of difficult intubation defined as more than two attempts or failed intubation. Results During the study period, 895 women were prospectively included in 17 maternity hospitals, accounting for 79% of women who had general anaesthesia for non-elective Caesarean section. Maternal hypoxaemia was observed in 172 women (19%; confidence interval [CI], 17–22%). Risk factors associated with hypoxaemia in the multivariate analysis were difficult or failed intubation (adjusted odds ratio [aOR]=19.1 [8.6–42.7], P 35 kg m−2 (aOR=0.53 [0.28–0.998], P=0.0495). Intubation was difficult in 40 women (4.5%; CI, 3.3–6%) and failed intubation occurred in five women (0.56%; CI, 0.1–1%). In the multivariate analysis, use of a hypnotic drug other than propofol was associated with difficult or failed intubation (aOR=25 [2–391], P=0.02). A propensity score confirmed that propofol was associated with a significant decreased risk of difficulty or failure to intubate (P Conclusions Hypoxaemia during Caesarean sections was observed in 19% of women and was significantly associated with difficult or failed intubation. The use of propofol may protect against the occurrence of difficult intubation.

ImportanceInformation about the severity of Omicron is scarce.ObjectiveTo report the respective risk of ICU admission in patients hospitalized with Delta and Omicron variants and to compare the characteristics and disease severity of critically ill patients infected with both variants according to vaccination status.DesignAnalysis from the APHP database, called Reality, prospectively recording the following information in consecutive patients admitted in the ICU for COVID-19: age, sex, immunosuppression, vaccination, pneumonia, need for invasive mechanical ventilation, time between symptom onset and ICU admission, and in-ICU mortality. Retrospective analysis on an administrative database, “Système d’Information pour le Suivi des Victimes” (SI-VIC), which lists hospitalized COVID-19 patients.Setting39 hospitals in the Paris area from APHP group.ParticipantsPatients hospitalized from December 1, 2021 to January 18, 2022 for COVID-19.Main outcomes and measuresRisk of ICU admission was evaluated in 3761 patients and Omicron cases were compared to Delta cases in the ICU in 888 consecutive patients.ResultsOn January 18, 45% of patients in the ICU and 63.8% of patients in conventional hospital units were infected with the Omicron variant (p < 0.001). The risk of ICU admission with Omicron was reduced by 64% than with Delta (9.3% versus 25.8% of cases, respectively, p < 0.001). In critically ill patients, 400 had the Delta variant, 229 the Omicron variant, 98 had an uninformative variant screening test and 161 did not have information on variant screening test. 747 patients (84.1%) were admitted for pneumonia. Compared to patients infected with Delta, Omicron patients were more vaccinated (pConclusion and relevanceCompared to the Delta variant, the Omicron variant is less likely to result in ICU admission and less likely to be associated with pneumonia. However, when patients with the Omicron variant are admitted for pneumonia, the severity seems similar to that of patients with the Delta variant, with more immunocompromised and vaccinated patients and no difference in adjusted in-ICU mortality. Further studies are needed to confirm our results.

International audience; No abstract available

Thromboembolic events may occur both during and after pregnancy Pregnancy in itself increases the thromboembolic risk, which is even greater during the postpartum period Due to additional coagulation changes induced by COVID-19 infection, this risk may even be greater

International audience; Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.

International audience; BACKGROUND: To determine the efficacy and safety of intravenous postoperative morphine titration in the elderly compared with younger patients. METHODS: In the post-anaesthesia care unit, patients complaining of pain received morphine until adequate pain relief. Intravenous morphine was titrated as 3 mg boluses in young (age 65 yr) and 2 mg in elderly patients (>65 yr) every 5 min. RESULTS: We studied 350 young and 68 elderly patients. There were no significant differences between the two age groups for pain intensity at the onset of titration (numerical rating scale, 7.4 +/- 1.7 in young vs. 7.5 +/- 1.7 in elderly patients), area under the curve of numerical rating scale vs. morphine boluses (97.7 +/- 59.6 vs. 98.2 +/- 62), number of boluses required to obtain pain relief (3 +/- 1.3 vs. 3 +/- 1.3), percentage of titration failures (10% vs. 9%) and incidence of excessive sedation (18% vs. 21%). Renal clearance was significantly reduced in elderly compared with young patients (55 +/- 21 vs. 85 +/- 15 mL min(-1); P < 0.0001). CONCLUSION: Using lower bolus doses, pain relief in the immediate postoperative period with morphine was as efficacious and safe in elderly patients as in younger patients. The decrease in renal clearance of morphine in the elderly justifies the reduction of intravenous morphine boluses for the treatment of postoperative pain.

Use of morphine by titration in the post-anaesthesia care unit (PACU) is often the first step in postoperative pain management. This approach provides rapid analgesia but shows a wide inter-individual variability in morphine requirements and may prolong patient stay in the PACU. The aim of this study was to identify the patient characteristics, surgical, anaesthetic, and postoperative factors predictive of early morphine requirements. The study included 149 patients undergoing various non-cardiac surgical procedures under general anaesthesia. In the multiple regression analysis of nine variables, only ethnicity (Caucasian), emergency surgery, major surgery, surgery exceeding 100 min, and pain score on arrival in PACU were predictive factors of morphine requirements. This observational study identifies for the first time independent predictive factors of morphine requirements in the early postoperative period. Future studies are warranted to evaluate the impact of intervention on these factors and any resulting improvement in postoperative pain treatment.

Background Dopamine (DA) is released in large amounts during cerebral ischemia and may exacerbate tissue damage. Riluzole (54274 RP) is a recently developed agent that depresses glutamate neurotransmission in the central nervous system (CNS) and that may protect against ischemic injury in some animal models. Because glutamate stimulates the release of DA in the striatum, the authors hypothesized that riluzole could antagonize DA release in this structure. Methods Assay for DA release consisted of superfusing 3H-DA preloaded synaptosomes with artificial cerebrospinal fluid (1 ml/min, 37 degrees C) and measuring the radioactivity obtained from 1-min fractions over 22 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with riluzole (0.1-100 microM, 5 min), and finally with no pharmacologic stimulation (9 min). The following depolarizing agents were tested: KCl (9, 15 mM), veratridine (0.01-1 microM), N-methyl-D-aspartate (NMDA, 0.1-1 mM), kainate (0.1-1 mM), and nicotine (0.01-0.5 mM). Assay for DA uptake was performed by measuring the radioactivity incorporated in synaptosomes incubated with 3H-DA (44 nM; 5 min; 37 degrees C). Results All depolarizing agents produced a significant, concentration-related increase from basal 3H-DA release. Riluzole was found to decrease the release induced by veratridine (1 microM), NMDA (1 mM), and kainate (1 mM) in a significant, concentration-related manner (IC50 = 9.5 microM, 1.6 microM, and 5.8 microM for veratridine, NMDA, and kainate, respectively). In contrast, it did not affect the release elicited by either KCl or nicotine. Riluzole had no significant effect on the specific 3H-DA uptake. Conclusions Riluzole produced a potent blockade of the release of DA mediated by activation of presynaptic sodium channels, NMDA, and kainate receptors. Depression of glutamate transmission together with blockade of DA release may contribute to the actions of this agent in vivo.

Background General anesthetics are thought to produce their hypnotic effects mainly by acting at ligand-gated ionic channels in the central nervous system (CNS). Although it is well established that volatile anesthetics significantly modify the activity of the acetylcholine nicotinic receptors of the neuromuscular junction, little is known about their actions on the acetylcholine receptors in the CNS. In this study, the effects of halothane and isoflurane on the regulation of dopamine (DA) (gamma-aminobutyric acid [GABA]) depolarization-evoked release mediated by nicotinic (muscarinic) presynaptic receptors were studied in the rat striatum. Methods Assay for GABA (dopamine) release consisted of 3H-GABA (3H-DA)-preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml/min, 37 degrees C) and measuring the radioactivity obtained from 1-min fractions for 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with vaporized halothane and isoflurane (0.5-5%, 5 min), and finally with no pharmacologic stimulation (5 min). The depolarizing agents were potassium chloride (KCl; 9 mM) alone or with acetylcholine (10(-6)-10(-4) M) and/or atropine (10(-5) M) for experiments with 3H-GABA, and KC1 (15 mM) and nicotine (10(-7) - 5 x 10(-4) M) alone or with mecamylamine (10(-5) M) for experiments with 3H-DA. Results Potassium chloride induced a significant, Ca(2+)-dependent release of both 3H-GABA and 3H-DA. Nicotine produced a concentration-related, mecamylamine-sensitive 3H-DA release that was significantly attenuated by nicotine (10(-7) M) preincubation. Acetylcholine elicited a dose-dependent, atropine-sensitive reduction of the KC1-evoked 3H-GABA release. Halothane and isoflurane significantly decreased the nicotine-evoked 3H-DA release but had only limited depressant effects on the KC1-stimulated 3H-DA and no action on the KC1-induced 3H-GABA release. The effects of acetylcholine on 3H-GABA release were reversed by halothane but not by isoflurane. Conclusions Clinically relevant concentrations of halothane and isoflurane significantly, but differentially, alter the presynaptic cholinergic regulation of the release of inhibitory neurotransmitters in the striatum. These results suggest that the cholinergic transmission may represent an important and specific presynaptic target for volatile anesthetics in the CNS.

An increase in Mallampati class is associated with difficult laryngoscopy in obstetrics. The goal of our study was to determine the changes in Mallampati class before, during, and after labour, and to identify predictive factors of the changes.Mallampati class was evaluated at four time intervals in 87 pregnant patients: during the 8th month of pregnancy (T(1)), placement of epidural catheter (T(2)), 20 min after delivery (T(3)), and 48 h after delivery (T(4)). Factors such as gestational weight gain, duration of first and second stages of labour, and i.v. fluids administered during labour were evaluated for their predictive value. Mallampati classes 3 and 4 were compared for each time interval. Logistic regression was used to test the association between each factor and Mallampati class evolution.Mallampati class did not change for 37% of patients. The proportion of patients falling into Mallampati classes 3 and 4 at the various times of assessment were: T(1), 10.3%; T(2), 36.8%; T(3), 51.7%; and T(4), 20.7%. The differences in percentages were all significant (P0.01). None of the evaluated factors was predictive.The incidence of Mallampati classes 3 and 4 increases during labour compared with the pre-labour period, and these changes are not fully reversed by 48 h after delivery. This work confirms the absolute necessity of examining the airway before anaesthetic management in obstetric patients.

Urinary retention is a common postoperative complication associated with bladder overdistension and the risk of permanent detrusor damage. The goal of this study was to determine predictive factors of early postoperative urinary retention in the postanesthesia care unit (PACU). We prospectively collected, in 313 adult patients, variables including age, gender, previous history of urinary tract symptoms, type of surgery and anesthesia, intraoperative administration of anticholinergics, amount of intraoperative fluids, IV morphine titration, and bladder volume on entry to the PACU. For each patient, bladder volume was measured by ultrasound on entry and before discharge from the PACU. Urinary retention was defined as a bladder volume larger than 600 mL with an inability to void within 30 min. Predictive factors were identified by multivariate analysis. The incidence of urinary retention in the PACU was 16%. In the multivariate analysis only the amount of intraoperative fluids (or=750 mL; P = 0.02; odds ratio = 2.3), age (or=50 yr; P = 0.008; odds ratio = 2.4), and bladder volume on entry to PACU (or=270 mL; P = 0.0001; odds ratio = 4.8) were found to independently increase the risk of urinary retention. Considering the clinical impact of undiagnosed postoperative urinary retention, these results suggest systematic evaluation of bladder volume with a portable ultrasound device in the PACU, especially in patients with risk factors.In this observational study, the ultrasound monitoring of bladder volume in the postanesthesia care unit (PACU) revealed that postoperative urinary retention occurred with an incidence of 16%. Age (or=50 yr), amount of intraoperative fluid volume (or=750 mL), and bladder volume on entry to PACU (or=270 mL) were independent predictive factors for this complication.

To determine the effectiveness of ip bupivacaine and/or morphine for postoperative analgesia after laparoscopic surgery. A controversy exists on the effectiveness and clinical value of ip injection of local anesthetics for postoperative analgesia. A possible peripheral analgesic effect of morphine after ip injection remains debated as well.We conducted a randomized, double-blinded, study to compare the efficacy of prophylactic ip administration of 0.9% saline (n = 16), 0.5% bupivacaine (100 mg, n = 15), morphine (3 mg, n = 16) and a mixture with 0.5% bupivacaine (100 mg) and morphine (3 mg, n = 18) to reduce both postoperative pain scores and analgesic requirements after gynecologic laparoscopic surgery. A multimodal analgesia regimen (acetaminophen, nonsteroidal anti-inflammatory drugs and morphine) was used for postoperative analgesia.No difference was observed in postoperative pain scores (visual analogue scale at rest and on coughing), or analgesic requirements during the first 24 postoperative hours between the four groups. There was also no significant intergroup difference in sedation scores and incidence of nausea and vomiting.When multimodal postoperative analgesia is used, prophylactic ip administration of 100 mg bupivacaine and/or 3 mg morphine does not significantly improve postoperative analgesia in patients undergoing laparoscopic gynecologic surgery.

Background The goal of this study was to evaluate the effectiveness on postoperative pain, and cognitive impact, of patient-controlled analgesia (PCA) compared with subcutaneous (s.c.) injections of morphine in elderly patients undergoing total hip replacement (THR). Methods Forty patients older than 70 yr were randomly assigned to two different postoperative analgesic techniques for 48 h: i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCA group) or regular s.c. morphine injections (SC group). Postoperative pain was assessed at rest and when moving, using a visual analogue scale (VAS) every 4 h. A Mini Mental Status (MMS) examination was used to assess cognitive functions before surgery, at 2 h, 24 h and 48 h after surgery, and at hospital discharge. Side-effects were also recorded systematically during the first 48 h after surgery. Results The PCA group showed significantly lower pain scores than the SC group both at rest and during mobilization. However, the clinical significance of pain scores was weak. There was no intergroup difference in postoperative MMS scores. The incidence of side-effects was similar in both groups. Conclusions We conclude that in healthy elderly subjects undergoing THR, the flexibility of the analgesic regimen is more important than the route of administration with regard to efficacy, adverse effects and recovery of cognitive function.

To compare recovery of psychomotor function in elderly and young surgical patients at emergence from propofol-alfentanil anaesthesia. Ten elderly (> 70 yr) and 10 younger ( 70 ans) et 10 jeunes patients (< 40 ans), dont la chirurgie orthopedique de moins de trois heures avait ete prevue, ont recu une anesthesie avec du protoxyde d’azote, du propofol et de l’alfentanil. On a enregistre les doses cumulatives de propofol et d’alfentanil, le temps entre l’arret de la perfusion de propofol et l’ouverture des yeux (OY), d’apres une commande verbale, et le moment de l’extubation. Le rendement psychomoteur a ete evalue par le test MMS de Folstein et coll. (Mini-Mental State) administre le jour precedent la chirurgie et, apres la chirurgie, 30, 60 et 120 min. apres l’extubation. Les concentrations sanguines de propofol ont ete mesurees a l’OY et a chaque tâche du test MMS. Les rendements au MMS preoperatoire; la duree de la chirurgie et de l’anesthesie et les doses cumulatives de propofol et d’alfentanil etaient comparables entre les jeunes patients et les patients âges. Les rendements MMS postoperatoires ont ete plus bas a 30, 60 et 120 min chez les patients âges. Les concentrations sanguines de propofol n’etaient pas differents entre les deux groupes de patients a l’OY, et a 30, 60 et 120 min. Le rendement psychomoteur est altere chez les patients âges par rapport aux jeunes patients au moment du reveil apres l’anesthesie au propofol et a l’alfentanil. On ne peut probablement pas relier ces differences a l’accumulation de propofol chez les patients âges.

The importance of malaria as a cause of anemia in pregnancy in endemic areas remains controversial. The prevalence of anemia in pregnant women following the dry (May) and the rainy (November) seasons was compared in two successive years in Bougoula village (region of Sikasso, Mali). Phase I (1992) was observational and included 172 pregnant women and 208 controls. In Phase II (1993, 174 pregnant women and 206 controls), malaria prophylaxis with proguanil (200 mg/day) and chloroquine (300 mg/week) was offered to pregnant women. A strong seasonal variation in the prevalence of moderate to severe anemia in pregnant women (hematocrit < 30%) occurred in Phase I (dry season = 8.7%, rainy season = 41.2%). This variation was present only in women of parity lower than five, and paralleled variation in parasitemia. In Phase II, the seasonal variation of anemia was suppressed in women under malaria prophylaxis (presence of antimalarial metabolites in urine), and the overall prevalence of moderate to severe anemia in pregnancy decreased by 55.5% (22.8-74.3%). We conclude that malaria is the major cause of anemia in pregnancy in this region. A high priority should be given to prevention of malaria in pregnancy.

We have examined the effects of ketamine, etomidate, propofol and thiopentone on the uptake of [3H]-dopamine into rat striatal synaptosomes. [3H]-dopamine uptake (5 min, 37 degrees C) was potently inhibited by nomifensine, a classical inhibitor of the dopamine carrier. All anaesthetics induced concentration-related inhibition of the uptake process, values for IC50 being 4.6 x 10(-6), 5.5 x 10(-5), 1.5 x 10(-4) and 2.7 x 10(-4) mol litre-1 for ketamine, etomidate, propofol and thiopentone, respectively. For all anaesthetics, inhibition of [3H]-dopamine uptake was reversible with a non-competitive profile. These data suggest that inhibition of striatal dopamine uptake may represent a relevant target site for some, but not all, i.v. anaesthetics.

Introduction Our purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss. Methods This was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures. Results A total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P = 0.03). Conclusions This study is the first to demonstrate that high-dose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH. Trial registration Controlled Trials ISRCTN09968140.

Background Experimental data suggest that volatile anesthetics induce significant changes in extracellular dopamine concentrations in the striatum, a restricted but functionally important brain area. In the present study, the authors used a superfused slice preparation to examine the effects of halothane and isoflurane on both spontaneous and N-methyl-D-aspartate (NMDA)-evoked dopamine release in the striatum, and whether these effects involved actions of these anesthetics mediated by gamma-aminobutyric acid receptors in this structure. Methods Radioactivity collected from 5-min fractions was compared in the absence (basal release) or presence (evoked release) of NMDA alone and combined with various pharmacologic or anesthetic agents in slices of the dorsolateral striatum and synaptosomes of the whole striatum preloaded with 3H-dopamine and superfused with artificial cerebrospinal fluid. Results In tetrodotoxin-treated striatal slices, halothane and isoflurane significantly increased dopamine basal release (EC50 = 0.33 mM and 0.41 mM for halothane and isoflurane, respectively). Both agents decreased the NMDA-evoked dopamine release in both the absence (IC50 = 0.15 mM and 0.14 mM for halothane and isoflurane, respectively) and presence (IC50 = 0.15 mM for both halothane and isoflurane) of tetrodotoxin in slices, and in synaptosomes (IC50 = 0.19 mM for both halothane and isoflurane). NMDA-induced dopamine release was significantly enhanced by bicuculline, a gamma-aminobutyric acid receptor antagonist. Halothane and isoflurane inhibitory effects on NMDA-evoked dopamine release were significantly reduced in the presence of bicuculline. Conclusion These results indicate that halothane and isoflurane decrease the NMDA-evoked dopamine release by acting directly at dopamine terminals in striatal slices. They support the involvement of both depression of presynaptic NMDA receptor-mediated responses and enhancement of gamma-aminobutyric acid receptor-mediated responses in these effects.

Background Prompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented. Methods Clinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3–4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines. Results Among the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79–1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines. Conclusions An etCO2 value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine. Clinical trial registration NCT01637220.