Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial).

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) affects up to 30% of patients, increasing morbidity and healthcare costs. This condition results from complex factors like ischemia-reperfusion injury and renal hemodynamic changes, often exacerbated by surgical procedures. Norepinephrine, commonly used in cardiac surgeries, may heighten the risk of CS-AKI. In contrast, vasopressin, a noncatecholaminergic agent, shows potential in preserving renal function by favorably affecting renal hemodynamic. Preliminary findings, suggest vasopressin could reduce the incidence of CS-AKI compared to norepinephrine. Additionally, vasopressin is linked to a lower incidence of postoperative atrial fibrillation, another factor contributing to longer hospital stays and higher costs. This study hypothesizes that vasopressin could effectively reduce CS-AKI occurrence and severity by optimizing renal perfusion during cardiac surgeries. STUDY DESIGN: The NOVACC trial (NCT05568160) is a multicenter, randomized, double blinded superiority-controlled trial testing the superiority of vasopressin over norepinephrine in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB). The primary composite end point is the occurrence of acute kidney injury and death. The secondary end points are neurological, cardiologic, digestive, and vasopressor related complications at day 7, day 30, day 90, hospital and intensive care unit lengths of stay, medico-economic costs at day 90. CONCLUSION: The NOVACC trial will assess the effectiveness of vasopressin in cardiac surgery with CPB in reducing acute kidney injury, mortality, and medical costs. CLINICAL TRIAL REGISTRATION: NCT05568160.

Anaphylaxis mortality in the perioperative setting: Epidemiology, elicitors, risk factors and knowledge gaps.

Perioperative anaphylaxis (PA) is a severe condition that can be fatal, but data on PA mortality are scarce. The aim of this article is to review the epidemiology, elicitors and risk factors for PA mortality and identify knowledge gaps and areas for improvement regarding the management of severe PA. PA affects about 100 cases per million procedures. Mortality is rare, estimated at 3 to 5 cases per million procedures, but the PA mortality rate is higher than for other anaphylaxis aetiologies, at 1.4% to 4.8%. However, the data are incomplete. Published data mention neuromuscular blocking agents and antibiotics, mainly penicillin and cefazolin, as the main causes of fatal PA. Reported risk factors for fatal PA vary in different countries. Most frequently occurring comorbidities are obesity, male gender, cardiovascular diseases and ongoing treatment with beta-blockers. However, there are no clues about how these factors interact and the impact of individual risk factors. The pathophysiology of fatal PA is still not completely known. Genetic factors such as deficiency in PAF-acetyl hydrolase and hereditary alpha-tryptasemia, have been reported as modulators of severe anaphylaxis and possible targets for specific treatments. Our review underlines unmet needs in the field of fatal PA. Although we confirmed the need for timely administration of an adequate dose of adrenaline and the proper infusion of fluids, there is no evidence-based data on the proper dose of intravenous titrated adrenaline and which clinical manifestations would flag the need for fluid therapy. There are no large clinical studies supporting the administration of alternative vasopressors, such as glucagon and methylene blue. Further research on pathophysiological mechanisms of PA and its severity may address these issues and help clinicians to define new therapeutic approaches.

Changes in Practices After Implementation of a Patient Blood Management Program in French Surgical Departments: The National Multicenter Observational PERIOPES Study.

BACKGROUND: Patient blood management (PBM) is an evidence-based approach recommended to improve patient outcomes. Change in practices is often challenging. We report here data from French surgical departments before and after a standardized implementation of a PBM program. METHODS: This was a national, multicenter, observational study in surgical centers ("expert" centers with an already established protocol for preoperative anemia or "pilot" centers). Data from consecutive surgical patients of different specialties were retrieved before and after the implementation of a PBM program. Primary outcome variables (preoperative anemia treatment rates, transfusion rates, and length of hospital stay) before and after the implementation of a PBM program were analyzed with segmented regression adjusted on confounders (American Society of Anesthesiologists [ASA] scores and centers). RESULTS: A total of 1618 patients (ASA physical status III and IV, 38% in the first period and 45% in the second period) were included in expert (N = 454) or pilot (N = 1164) centers during the first period (January 2017-August 2022) and 1542 (N = 440 and N = 1102, respectively) during the second period (January 2020-February 2023). After implementation of the PBM program, the rate of preoperative anemia treatment increased (odds ratio, 2.37; 95% confidence interval [CI], 1.20-4.74; P = .0136) and length of hospital stay in days decreased (estimate, -0.11; 95% CI, -0.21 to -0.02; P = .0186). Transfusion rate significantly decreased only in expert centers (odds ratio, 0.17; 95% CI, 0.03-0.88; P = .0354). CONCLUSIONS: PBM practices in various surgical specialties improved significantly after the implementation of a PBM program. However, too many patients with preoperative anemia remained untreated.

NButGT Reinforces the Beneficial Effects of Epinephrine on Cardiac Mitochondrial Respiration, Lactatemia and Cardiac Output in Experimental Anaphylactic Shock.

Anaphylactic shock (AS) is the most severe form of acute systemic hypersensitivity reaction. Although epinephrine can restore patients' hemodynamics, it might also be harmful, supporting the need for adjuvant treatment. We therefore investigated whether NButGT, enhancing O-GlcNAcylation and showing beneficial effects in acute heart failure might improve AS therapy. Ovalbumin-sensitized rats were randomly allocated to six groups: control (CON), shock (AS), shock treated with NButGT alone before (AS+pre-Nbut) or after (AS+post-Nbut) AS onset, shock treated with epinephrine alone (AS+EPI) and shock group treated with combination of epinephrine and NButGT (AS+EPI+preNBut). Induction of shock was performed with an intravenous (IV) ovalbumin. Cardiac protein and cycling enzymes O-GlcNAcylation levels, mean arterial pressure (MAP), heart rate, cardiac output (CO), left ventricle shortening fraction (LVSF), mitochondrial respiration, and lactatemia were evaluated using Western blotting experiments, invasive arterial monitoring, echocardiography, mitochondrial oximetry and arterial blood samples. AS decreased MAP (-77%, p < 0.001), CO (-90%, p < 0.001) and LVSF (-30%, p < 0.05). Epinephrine improved these parameters and, in particular, rats did not die in 15 min. But, cardiac mitochondrial respiration remained impaired (complexes I + II -29%, p < 0.05 and II -40%, p < 0.001) with hyperlactatemia. NButGT pretreatment (AS+pre-Nbut) efficiently increased cardiac O-GlcNAcylation level as compared to the AS+post-Nbut group. Compared to epinephrine alone, the adjunction of NButGT significantly improved CO, LVSF and mitochondrial respiration. MAP was not significantly increased but lactatemia decreased more markedly. Pretreatment with NButGT increases O-GlcNAcylation of cardiac proteins and has an additive effect on epinephrine, improving cardiac output and mitochondrial respiration and decreasing blood lactate levels. This new therapy might be useful when the risk of AS cannot be avoided.

Perioperative individualized hemodynamic optimization according to baseline mean arterial pressure in cardiac surgery patients: Rationale and design of the OPTIPAM randomized trial.

BACKGROUND: Postoperative morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB) remain high despite recent advances in both anesthesia and perioperative management. Among modifiable risk factors for postoperative complications, optimal arterial pressure during and after surgery has been under debate for years. Recent data suggest that optimizing arterial pressure to the baseline of the patient may improve outcomes. We hypothesize that optimizing the mean arterial pressure (MAP) to the baseline MAP of the patient during cardiac surgery with CPB and during the first 24 hours postoperatively may improve outcomes. STUDY DESIGN: The OPTIPAM trial (NCT05403697) will be a multicenter, randomized, open-label controlled trial testing the superiority of optimized MAP management as compared with a MAP of 65 mm Hg or more during both the intraoperative and postoperative periods in 1,100 patients scheduled for cardiac surgery with CPB. The primary composite end point is the occurrence of acute kidney injury, neurological complications including stroke or postoperative delirium, and death. The secondary end points are hospital and intensive care unit lengths of stay, Day 7 and Day 90 mortality, postoperative cognitive dysfunction on Day 7 and Day 90, and quality of life at Day 7 and Day 90. Two interim analyses will assess the safety of the intervention. CONCLUSION: The OPTIPAM trial will assess the effectiveness of an individualized target of mean arterial pressure in cardiac surgery with CPB in reducing postoperative morbidity. CLINICAL TRIAL REGISTRATION: NCT05403697.

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.

Evaluation of Anemia and Iron Deficiency in French Surgical Departments: The National Multicenter Observational PERIOPES Study.

BACKGROUND: Assessment of anemia and iron deficiency before surgery is pivotal for patient blood management (PBM), but few data on current practices are available in the French context. The objective of this study was to describe anemia and iron deficiency management and blood transfusion use in surgical departments in France. METHODS: This was a national multicenter cross-sectional study in 13 public hospitals and 3 private ones (all with an interest for PBM). Data of consecutive surgical patients from different specialties were retrieved from their chart between July 30, 2019, and December 31, 2021. Data included hemoglobin, iron workup, treatment with oral/intravenous iron or erythropoiesis-stimulating agent, and transfusions. RESULTS: Data from 2345 patients (median age, 68 years; women, 50.9%; American Society of Anesthesiologists [ASA] physical status III-IV, 35.4%) were obtained. Only 5 centers had a formalized PBM program. At preoperative anesthesia visit, hemoglobin (Hb) level was assessed in 2112 (90.1%) patients and anemia diagnosed in 722 of them (34.2%). Complete iron workup was performed in 715 (30.5%) of the 2345 patients. Iron deficiency anemia was present in 219 (30.3%) of the 722 anemic patients. Among patients with anemia, only 217 (30.1%) of them were treated. A total of 479 perioperative blood transfusions were reported in 315 patients. Restrictive transfusion was not applied in 50% of transfusion episodes, and the single-unit red blood cell transfusion was also not frequent (37.2%). CONCLUSIONS: Our observational study showed that preoperative anemia was frequent, but iron deficiency was often not assessed and few patients were treated. There is an urgent need for PBM implementation in these centers.

Cerebral perfusion using ASL in patients with COVID-19 and neurological manifestations: A retrospective multicenter observational study.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.

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.

Doppler study of portal vein and renal venous velocity predict the appropriate fluid response to diuretic in ICU: a prospective observational echocardiographic evaluation.

BACKGROUND: Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion. METHODS: The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients' characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion. RESULTS: Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI95%:0.70-0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI95% 0.61-0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI95% 0.53-0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion. CONCLUSION: The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies.

Epidemiology of perioperative anaphylaxis in the United States: new insights but more to learn and do.

Gonzalez-Estrada and colleagues report an estimated risk of severe or fatal perioperative anaphylaxis of one in 6,825 procedures during the period 2005-2014. This is slightly higher than that reported previously in France and England. Several predictors of near-fatal and fatal reactions are identified, such as increased age, cancer, and congestive cardiac failure.

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

BACKGROUND: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings. METHODS: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed. RESULTS: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%). CONCLUSIONS: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.

Impact of COVID-19 and lockdown regarding blood transfusion.

BACKGROUND: The outbreak of a SARS-CoV-2 resulted in a massive afflux of patients in hospital and intensive care units with many challenges. Blood transfusion was one of them regarding both blood banks (safety, collection, and stocks) and consumption (usual care and unknown specific demand of COVID-19 patients). The risk of mismatch was sufficient to plan blood transfusion restrictions if stocks became limited. STUDY DESIGN AND METHODS: Analyses of blood transfusion in a tertiary hospital and blood collection in the referring blood bank between February 24 and May 31, 2020. RESULTS: Withdrawal of elective surgery and non-urgent care and admission of 2291 COVID-19 patients reduced global activity by 33% but transfusion by 17% only. Only 237 (10.3) % of COVID-19 patients required blood transfusion, including 45 (2.0%) with acute bleeding. Lockdown and cancellation of mobile collection resulted in an 11% reduction in blood donation compared to 2019. The ratio of reduction in blood transfusion to blood donation remained positive and stocks were slightly enhanced. DISCUSSION: Reduction of admissions due to SARS-CoV-2 pandemic results only in a moderate decrease of blood transfusion. Incompressible blood transfusions concern urgent surgery, acute bleeding (including some patients with COVID-19, especially under high anticoagulation), or are supportive for chemotherapy-induced aplasia or chronic anemia. Lockdown results in a decrease of blood donation by cancellation of mobile donation but with little impact on a short period by mobilization of usual donors. No mismatch between demand and donation was evidenced and no planned restriction to blood transfusion was necessary.

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.

Decompressive hemicraniectomy for acute ischemic stroke in a patient implanted with a left ventricular assist device: a case report.

BACKGROUND: Thromboembolic ischemic stroke (IS) is one of the most feared complications of left ventricular assist device (LVAD) placement and represents a challenge to surgical management because of concomitant anticoagulant therapy. CASE PRESENTATION: A 39-year-old man presented with cardiogenic shock following an out-of-hospital cardiac arrest. After a period of stabilization, the patient was referred for LVAD placement. Upon recovery from anesthesia, he presented with acute neurological deficits suggestive of IS. A brain computed tomography confirmed the diagnosis, and an emergency decompressive hemicraniectomy (DHC) was performed. Anticoagulation was managed empirically. The patient's neurological status progressively improved and he was referred for heart transplantation at five months from DHC. One month later, cranioplasty was performed. CONCLUSIONS: This report suggests an anticoagulation management approach in combination with decompressive craniectomy after IS in a patient with LVAD placement was successful. An optimized anticoagulation management and collaborative team-based practice may contribute to successful outcomes in complex cases.

An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.

Molecular mechanisms and pathophysiology of perioperative hypersensitivity and anaphylaxis: a narrative review.

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation. The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases.

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.