The Effects of Acute and Chronic Inflammation on the Dynamics of Fluid Shift of Ringer's Solution and Hemodynamics during Surgery.

The aim of this study was to investigate the influences of acute and chronic inflammation on the dynamics of fluid shift of Ringer's solution and hemodynamics in patients during surgery. Thirty-seven patients with the American Society of Anesthesiologists (ASA) grades I-II were enrolled and allocated to two study groups according to the type of disease and operation and inflammation, including patients undergoing emergency appendectomy (Acute group, n = 19) and patients undergoing elective cholecystectomy (Chronic group, n = 18). All of the patients were administered 15 mL/kg of Ringer's lactated (LR) solution at a constant rate over 35 min before the induction of anesthesia. Plasma dilution (PD), volume expansion (VE), volume expansion efficiency (VEE), and extravascular volume (EVV) were calculated based on the concentration of hemoglobin within 2 h post-infusion. Heart rate (HR), arterial blood pressure and urine output were also recorded. PD and VE peaked at the end of infusion, while VEE peaked at the beginning of infusion in all of the patients. After infusion, PD, VE and VEE in the Acute group were all higher than those in the Chronic group (p < 0.05). PD and VE were higher during anesthesia or surgery than during awake or non-surgery (p < 0.001). The mean arterial pressure (MAP) and diastolic pressure (DBP) in the Acute group were significantly lower (p < 0.001) and HR was significantly higher (p < 0.001) than in the Chronic group during the study periods. It was suggested that patients with acute inflammation be treated with individualized fluid therapy during surgery.

Integrating basophil activation tests into evaluation of perioperative anaphylaxis to neuromuscular blocking agents.

BACKGROUND: Neuromuscular blocking agents (NMBAs) remain the leading cause of perioperative anaphylaxis in Australia. Standard evaluation comprises history, skin tests, and in vitro specific immunoglobulin E tests. Drug provocation tests to suspected NMBA culprits are associated with a significant risk. Basophil activation testing (BAT) is a potentially useful in vitro test that is not commercially available in Australia or as part of standard evaluation. METHODS: All patients attending the Anaesthetic Allergy Clinic in Sydney, Australia between May 2017 and July 2018 exposed to an NMBA before the onset of anaphylaxis during their anaesthetic qualified for the study. We recruited 120 patients sequentially who received standard evaluation plus BAT using CD63, CD203c, and CD300a as surface activation markers. RESULTS: BAT results were expressed as % upregulation above the negative control and stimulation index (mean fluorescence index of stimulated sample divided by the negative control). We calculated cut-offs of 4.45% and 1.44 for CD63, and 8.80% and 1.49 for CD203c, respectively. Sensitivity was 77% with specificity of 76%. A subgroup of 10 patients with NMBA anaphylaxis had no sensitisation on skin tests. BAT using CD63 and CD203c showed sensitisation in six of these 10, and adding CD300a identified sensitisation in nine patients. BAT was positive in seven of nine patients with anaphylaxis of unknown aetiology. CONCLUSIONS: BAT may be a useful supplement to the standard evaluation in diagnosing NMBA anaphylaxis in patients with suggestive histories, but no sensitisation on skin tests. Ongoing study of this specific group of patients is required to clarify its utility in clinical practice.

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.

Perioperative Inflammation and Its Modulation by Anesthetics.

Surgery and other invasive procedures, which are routinely performed during general anesthesia, may induce an inflammatory response in the patient. This inflammatory response is an inherent answer of the body to the intervention and can be both beneficial and potentially harmful. The immune system represents a unique evolutionary achievement equipping higher organisms with an effective defense mechanism against exogenous pathogens. However, not only bacteria might evoke an immune response but also other noninfectious stimuli like the surgical trauma or mechanical ventilation may induce an inflammatory response of varying degree. In these cases, the immune system activation is not always beneficial for the patients and might carry the risk of concomitant, harmful effects on host cells, tissues, or even whole organ systems. Research over the past decades has contributed substantial information in which ways surgical patients may be affected by inflammatory reactions. Modulations of the patient's immune system may be evoked by the use of anesthetic agents, the nature of surgical trauma and the use of any supportive therapy during the perioperative period. The effects on the patient may be manifold, including various proinflammatory effects. This review focuses on the causes and effects of inflammation in the perioperative period. In addition, we also highlight possible approaches by which inflammation in the perioperative may be modulated in the future.

Recombinant Slit2 attenuates neuroinflammation after surgical brain injury by inhibiting peripheral immune cell infiltration via Robo1-srGAP1 pathway in a rat model.

BACKGROUND AND PURPOSE: Peripheral immune cell infiltration to the brain tissue at the perisurgical site can promote neuroinflammation after surgical brain injury (SBI). Slit2, an extracellular matrix protein, has been reported to reduce leukocyte migration. This study evaluated the effect of recombinant Slit2 and the role of its receptor roundabout1 (Robo1) and its downstream mediator Slit-Robo GTPase activating protein 1 (srGAP1)-Cdc42 on peripheral immune cell infiltration after SBI in a rat model. METHODS: One hundred and fifty-three adult male Sprague-Dawley rats (280-350 g) were used. Partial resection of right frontal lobe was performed to induce SBI. Slit2 siRNA was administered by intracerebroventricular injection 24h before SBI. Recombinant Slit2 was injected intraperitoneally 1h before SBI. Recombinant Robo1 used as a decoy receptor was co-administered with recombinant Slit2. srGAP1 siRNA was administered by intracerebroventricular injection 24h before SBI. Post-assessments included brain water content measurement, neurological tests, ELISA, Western blot, immunohistochemistry, and Cdc42 activity assay. RESULTS: Endogenous Slit2 was increased after SBI. Robo1 was expressed by peripheral immune cells. Endogenous Slit2 knockdown worsened brain edema after SBI. Recombinant Slit2 administration reduced brain edema, neurological deficits, and pro-inflammatory cytokines after SBI. Recombinant Slit2 reduced peripheral immune cell markers cluster of differentiation 45 (CD45) and myeloperoxidase (MPO), as well as Cdc42 activity in the perisurgical brain tissue which was reversed by recombinant Robo1 co-administration and srGAP1 siRNA. CONCLUSIONS: Recombinant Slit2 improved outcomes by reducing neuroinflammation after SBI, possibly by decreasing peripheral immune cell infiltration to the perisurgical site through Robo1-srGAP1 mediated inhibition of Cdc42 activity. These results suggest that Slit2 may be beneficial to reduce SBI-induced neuroinflammation.

Peri-operative adverse respiratory events in children.

Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse respiratory event should rely on clinical, rather than immunological, assessment.

Latex allergy on anaesthesiologist and anaesthesia managements: are the health workers high risk patients?

Anaphylaxis is defined as a severe, life threating, generalized or systemic hypersensitivity reaction. The most common agent involved in intraoperative anaphylactic reactions is muscle relaxant (61-70%); natural rubber latex (NRL) is the second most implicated agent and the incidence of latex-related anaphylactic reactions is increasing despite increasing awareness and preventive measures taken. Latex is a ubiquitous part of life today. Medical products which contain latex are present in our environment, especially in the hospital setting. This study focuses on our experience with two different anaesthetic techniques performed on the same patient who had latex hypersensitivity reaction and underwent surgery for myomectomy twice in 5 years. This case report aims to point out to latex hypersensitivity on health workers. The patient described had latex allergy and strategy of management during perioperative period is detailed.

[Correlation between pholcodine and perioperative anaphylaxis]. / Povezanost folkodina i perioperativne anafilaksije.

A large number of individuals experiencing anaphylactic reaction to neuromuscular blocking agents have not previously been in contact with them. The search for a substance inducing sensitization to muscle relaxants has led Norwegian and Swedish scientists to pholcodine, a cough suppressant, which is widely used in Europe and worldwide. Ammonium ion is an epitope common to pholcodine and neuromuscular blocking agents and it is the basis of their cross-reactivity. Based on the results of published studies that pointed to a connection of the use of pholcodine and perioperative anaphylactic reaction, pholcodine was withdrawn from the Norwegian market and subsequent research revealed a reduction of anaphylactic reactions in that country. In its latest report, the European Medicines Agency made a decision not to withdraw pholcodine mixtures from the market but it urged further research with the aim to clarify the cross-reactivity between pholcodine and neuromuscular blocking agents.

Reação anafilática induzida por látex em paciente submetido à apendicectomia aberta: relato de caso / Latex-induced anaphylactic reaction in a patient undergoing open appendectomy: case report / Reacción anafiláctica inducida por el látex en paciente sometido a la apendicectomía abierta: relato de caso

JUSTIFICATIVA E OBJETIVOS: Embora crescente a incidência de alergia ao látex na população em geral, eventos graves de anafilaxia durante alguns procedimentos cirúrgicos felizmente ainda são raros, porém com morbidade e mortalidade elevados. Não apenas a prevenção, mas o diagnóstico, o pronto tratamento e o acompanhamento dos pacientes acometidos por esse evento representam um desafio para o anestesiologista. O presente relato teve por objetivo descrever um caso de anafilaxia grave ao látex e discutir seu diagnóstico e tratamento. RELATO DO CASO: Paciente do sexo feminino, 39 anos, branca com suspeita diagnóstica de apendicite, é levada para procedimento de urgência sob raquianestesia. Aproximadamente 30 minutos após o início da cirurgia, apresentou quadro de anafilaxia com parada cardiorrespiratória, revertida após tratamento. Um dos cuidados foi o isolamento de eventuais agentes causais, sendo que, posteriormente, a paciente foi encaminhada para unidade de terapia intensiva e evoluiu sem sequelas. A dosagem de IgE-RAST (Radioallergosorbent Test) específico para o látex mostrou-se positiva. A paciente foi encaminhada para acompanhamento com o alergologista. CONCLUSÕES: O anestesiologista deve concentrar esforços na anamnese, mesmo em procedimentos de urgência, estando consciente das limitações que se apresentam nessas ocasiões. O prognóstico de anafilaxia depende do pronto início do tratamento adequado e o diagnóstico não se limita ao momento do evento, mas sim à determinação do fator causal. Criar um meio de acompanhar esses pacientes, a exemplo de outros centros internacionais, parece ser o caminho a ser seguido.

BACKGROUND AND OBJECTIVE: Despite the increase of latex allergy in general population, severe anaphylactic events during some surgical procedures are still rare; however, they are associated with increased morbidity and mortality. Prevention, diagnosis, treatment, and follow-up of patients affected by this event represent a challenge for anesthesiologists. The objective of this report was to describe a case of severe latex-induced anaphylactic reaction and discuss its diagnosis and treatment. CASE REPORT: This is a 39-year-old Caucasian female patient, with a diagnostic suspicion of appendicitis, who underwent an emergency surgery under spinal anesthesia. Approximately 30 minutes after beginning the surgery, the patient developed an anaphylactic reaction with cardiorespiratory arrest, which was reversed after treatment. Possible causative agents were isolated and, posteriorly, the patient was transferred to the intensive care unit, evolving without sequelae. Latex-specific IgE-RAST (Radioallergosorbent Test) was positive. The patient was referred to an allergist for follow-up. CONCLUSIONS: Anesthesiologists should focus on patient's history, even in urgent procedures, being aware of the limitations arising on these situations. The prognosis of anaphylaxis depends on prompt initiation of adequate treatment; diagnosis is not limited to the event occasion, but to the determination of the causative factor. Creating the means of following-up these patients, similar to other international centers, seems to be the example to be followed.

JUSTIFICATIVA Y OBJETIVOS: Aunque exista un aumento en la incidencia de alergia al látex en la población en general, los eventos graves de anafilaxia durante algunos procedimientos quirúrgicos por suerte todavía son raros, aunque con un nivel de morbilidad y mortalidad elevados. La prevención, el diagnóstico, el rápido tratamiento y el seguimiento de los pacientes afectados por ese evento, representan un reto para el anestesiólogo. El presente relato intentó describir un caso de anafilaxia grave al látex y discutir su diagnóstico y tratamiento. RELATO DEL CASO: Paciente del sexo femenino, 39 anos, blanca y con sospecha diagnóstica de apendicitis, que fue derivada a quirófano para un procedimiento urgente bajo raquianestesia. Aproximadamente 30 minutos después del inicio de la cirugía, presentó un cuadro de anafilaxia con parada cardiorrespiratoria, revertida posteriormente al tratamiento. Uno de los cuidados tomados fue el aislamiento de eventuales agentes causales, siendo que, posteriormente, la paciente fue derivada a la Unidad de Cuidados Intensivos y evolucionó sin secuelas. La dosificación de IgE-RAST (Radioallergosorbent Test), específico para el látex fue positiva. La paciente fue derivada para seguimiento con el alergista. CONCLUSIONES: El anestesiólogo debe concentrar sus esfuerzos en la anamnesis, aunque en los procedimientos de urgencia, sea consciente de las limitaciones que se presentan en esas ocasiones. El pronóstico de anafilaxia depende del rápido inicio del tratamiento adecuado, y el diagnóstico no se restringe al momento del evento, sino a la determinación del factor causal. Crear un medio de seguimiento para esos pacientes, como lo hacen otros centros internacionales, parece ser el camino que debe ser secundado.

[Latex-induced anaphylactic reaction in a patient undergoing open appendectomy. Case report]. / Reacción anafiláctica inducida por el látex en pacientesometido a la apendicectomía abierta. relato de caso.

BACKGROUND AND OBJECTIVE: Despite the increase of latex allergy in general population, severe anaphylactic events during some surgical procedures are still rare; however, they are associated with increased morbidity and mortality. Prevention, diagnosis, treatment, and follow-up of patients affected by this event represent a challenge for anesthesiologists. The objective of this report was to describe a case of severe latex induced anaphylactic reaction and discuss its diagnosis and treatment. CASE REPORT: This is a 39-year-old Caucasian female patient, with a diagnostic suspicion of appendicitis, who underwent an emergency surgery under spinal anesthesia. Approximately 30 minutes after beginning the surgery, the patient developed an anaphylactic reaction with cardiorespiratory arrest, which was reversed after treatment. Possible causative agents were isolated and, posteriorly, the patient was transferred to the intensive care unit, evolving without sequelae. Latex-specific IgE-RAST (Radioallergosorbent Test) was positive. The patient was referred to an allergist for follow-up. CONCLUSIONS: Anesthesiologists should focus on patient's history, even in urgent procedures, being aware of the limitations arising on these situations. The prognosis of anaphylaxis depends on prompt initiation of adequate treatment; diagnosis is not limited to the event occasion, but to the determination of the causative factor. Creating the means of following-up these patients, similar to other international centers, seems to be the example to be followed.

Differentiating the cellular and humoral components of neuromuscular blocking agent-induced anaphylactic reactions in patients undergoing anaesthesia.

BACKGROUND: The significance of IgE antibodies to neuromuscular blocking agent (NMBA)-induced anaphylactic reactions during anaesthesia is unclear. We investigated the relevance of IgE to rocuronium using an in vitro technique. METHODS: Serum samples from 61 patients with anaphylactic reactions during anaesthesia were investigated. On the basis of clinical history, allergy to NMBA was considered likely in 48 patients, further assessed using intradermal skin tests for several commonly used NMBAs, including rocuronium, vecuronium, and succinylcholine. To determine the presence of rocuronium IgE in human serum, a rocuronium-human serum albumin (rocHSA) conjugate was coupled to a solid phase and a radioallergosorbent test performed. The biological effects of patient serum NMBA-IgE on histamine release were investigated using in vitro sensitized basophils from healthy blood donors. RESULTS: IgE to rocuronium was found in 23 of 48 serum samples (48%) with NMBA allergy, although only two of these were able to sensitize basophils to release histamine in response to rocHSA. IgE-responsiveness in the basophil test was only observed with conjugated rocHSA and not with unconjugated rocuronium or the other NMBAs evaluated. However, unconjugated rocuronium inhibited the histamine release induced by rocHSA. Correlation between skin-test reactivity to rocuronium and IgE to rocHSA was low (P>0.1). In contrast, striking correlation between IgE to rocuronium and skin-test reactivity to succinylcholine was found (P<0.001). CONCLUSIONS: Our results indicate that NMBA-related anaphylaxis requires not only IgE NMBA reactivity, but also altered cellular reactivity in the patient. The latter may be demonstrable by testing basophils from the patient, a skin test with (steroidal) NMBA, or both.

Latex sensitization: a special risk for the obstetric population?

BACKGROUND: Previous studies have reported a greater frequency of sensitization to latex in the female population and a higher incidence of anaphylactic reactions to latex during cesarean section. In this study, the authors investigated the prevalence of latex sensitization in obstetric patients compared with nonpregnant subjects. METHODS: Two hundred ninety-four healthy pregnant women who were at term with a singleton fetus and scheduled for caesarean section (group A) were compared with 294 healthy nulliparous women with childbirth potential undergoing gynecologic surgery (group B). Before surgery, patients completed a questionnaire, and venous blood samples were collected to measure specific immunoglobulin E serum concentrations with a fluorescent enzyme immunoassay test. Skin-prick tests were performed if adverse reactions occurred during surgery. Latex allergy was diagnosed on the basis of immunoglobulin E results and/or positive skin-prick tests. RESULTS: The prevalence of latex sensitization was higher in group A than in group B (15/294, 5.1% vs. 5/294, 1.7%; P < 0.05). A significant difference in specific immunoglobulin E serum concentration was noted between pregnant and nonpregnant patients who had a positive fluorescent enzyme immunoassay test (median serum concentration: 1.93 kilounits/l; interquartile range = 2.28 vs. 0.78 kilounits/l; interquartile range = 1.07; P less than 0.05). Two patients in group A experienced an anaphylactic reaction to latex. Statistical analysis disclosed no association between latex sensitization and accepted risk factor for latex allergy. CONCLUSIONS: The authors report a higher prevalence of latex sensitization in the obstetric population than in nonpregnant subjects undergoing gynecologic surgery.