[Alpha-gal syndrome : Overview of clinical presentation and pathophysiology]. / Alpha-Gal-Syndrom : Ein Überblick zum klinischen Bild und zu pathophysiologischen Konzepten.

In the world of allergology, alpha-gal syndrome remains one of the most fascinating discoveries over the last 15 years as it is triggered by specific IgE directed against the immunogenic sugar galactose-α­1,3­galactose (alpha-gal), found foremost in mammalian meat, milk and products derived thereof, potentially resulting in anaphylaxis. Also, mammalian-derived drugs and medical products have been identified as possible culprits. Nonetheless, tick bites remain the major cause of specific alpha-gal-sIgE. Herein, we summarize the current clinical knowledge and pathophysiology of alpha-gal syndrome in order to better understand this disease.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Reliability of pressure waveform analysis to determine correct epidural needle placement in labouring women.

Pressure waveform analysis provides a reliable confirmatory adjunct to the loss-of-resistance technique to identify the epidural space during thoracic epidural anaesthesia, but its role remains controversial in lumbar epidural analgesia during labour. We performed an observational study in 100 labouring women of the sensitivity and specificity of waveform analysis to determine the correct location of the epidural needle. After obtaining loss-of-resistance, the anaesthetist injected 5 ml saline through the epidural needle (accounting for the volume already used in the loss-of-resistance). Sterile extension tubing, connected to a pressure transducer, was attached to the needle. An investigator determined the presence or absence of a pulsatile waveform, synchronised with the heart rate, on a monitor screen that was not in the view of the anaesthetist or the parturient. A bolus of 4 ml lidocaine 2% with adrenaline 5 µg.ml-1 was administered, and the epidural block was assessed after 15 min. Three women displayed no sensory block at 15 min. The results showed: epidural block present, epidural waveform present 93; epidural block absent, epidural waveform absent 2; epidural block present, epidural waveform absent 4; epidural block absent, epidural waveform present 1. Compared with the use of a local anaesthetic bolus to ascertain the epidural space, the sensitivity, specificity, positive and negative predictive values of waveform analysis were 95.9%, 66.7%, 98.9% and 33.3%, respectively. Epidural waveform analysis provides a simple adjunct to loss-of-resistance for confirming needle placement during performance of obstetric epidurals, however, further studies are required before its routine implementation in clinical practice.

Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on Inflammatory Response in Brain Dead Organ Donors.

BACKGROUND: Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. DESIGN: 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1ß, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. RESULTS: Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, p<0.01); the net decreases of pro-inflammatory cytokines, such as IL-6 and MCP-1, and the net increase of anti-inflammatory cytokine, such as IL-10, reached significant level in insulin treated donors compared with those in controls. CONCLUSION: High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice.

BACKGROUND: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. METHODS: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. RESULTS: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. CONCLUSIONS: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 1: pathophysiological considerations.

BACKGROUND: The present article has been written to convey concepts of anaesthetic care within the context of an Enhanced Recovery After Surgery (ERAS) programme, thus aligning the practice of anaesthesia with the care delivered by the surgical team before, during and after surgery. METHODS: The physiological principles supporting the implementation of the ERAS programmes in patients undergoing major abdominal procedures are reviewed using an updated literature search and discussed by a multidisciplinary group composed of anaesthesiologists and surgeons with the aim to improve perioperative care. RESULTS: The pathophysiology of some key perioperative elements disturbing the homoeostatic mechanisms such as insulin resistance, ileus and pain is here discussed. CONCLUSIONS: Evidence-based strategies aimed at controlling the disruption of homoeostasis need to be evaluated in the context of ERAS programmes. Anaesthesiologists could, therefore, play a crucial role in facilitating the recovery process.

The effect of chewing lidocaine soaked gauze on intubation conditions during awake videolaryngoscopy: a randomised controlled trial in the morbidly obese.

The increasing utilisation of the videolaryngoscope for awake tracheal intubation requires development and assessment of methods to decrease the gag reflex. We hypothesised that chewing gauze soaked with lidocaine would decrease the gag reflex during awake videolaryngoscope tracheal intubation. Twenty four morbidly obese patients assessed as having a potential difficult tracheal intubation were randomised to chew gauze soaked with 20 ml of 2% lidocaine or saline for 3 minutes. All patients then received 20 ml of aerosolised 2% lidocaine and underwent awake videolaryngoscope assisted tracheal intubation. Gagging scores, heart rate and blood pressure were assessed when best laryngeal view was obtained, when the tracheal tube was positioned at the cords, and when the tube was advanced into the trachea. In addition, serum lidocaine levels were measured. The primary outcome was the gagging score at best laryngeal visualisation, which was compared between groups with a Student's t-test. Gagging scores and hemodynamic parameters did not differ between groups, but the saline group had lower plasma levels of lidocaine after the intubation procedure. When used for awake videolaryngoscope assisted tracheal intubation of the morbidly obese, chewing lidocaine soaked gauze does not decrease the amount of gagging as compared to lidocaine aerosolisation, but does increase the plasma levels of lidocaine.

Randomized clinical trial of the impact of insulin therapy on liver function in patients undergoing major liver resection.

BACKGROUND: Postoperative liver dysfunction is the major source of morbidity and mortality in patients undergoing partial hepatectomy. This study tested the benefits of a metabolic support protocol based on insulin infusion, for reducing liver dysfunction following hepatic resection. METHODS: Consecutive consenting patients scheduled for liver resection were randomized to receive preoperative dextrose infusion followed by insulin therapy using the hyperinsulinaemic normoglycaemic clamp protocol (n = 29) or standard therapy (control group, n = 27). Patients in the insulin therapy group followed a strict dietary regimen for 24 h before surgery. Intravenous dextrose was started at 2 mg per kg per min the night before and continued until surgery. Hyperinsulinaemic therapy for a total of 24 h was initiated at 2 munits per kg per min at induction of anaesthesia, and continued at 1 munit per kg per min after surgery. Normoglycaemia was maintained (3.5-6.0 mmol/l). Control subjects received no additional dietary supplement and a conventional insulin sliding scale during fasting. All patients were tested serially to evaluate liver function using the Schindl score. Liver tissue samples were collected at two time points during surgery to measure glycogen levels. RESULTS: Demographics were similar in the two groups. More liver dysfunction occurred in the control cohort (liver dysfunction score range 0-8 versus 0-4 with insulin therapy; P = 0.031). Median (interquartile range) liver glycogen content was 278 (153-312) and 431 (334-459) µmol/g respectively (P = 0.011). The number of complications rose with increasing severity of postoperative liver dysfunction (P = 0.032) CONCLUSION: The glucose-insulin protocol reduced postoperative liver dysfunction and improved liver glycogen content. REGISTRATION NUMBER: NCT00774098 (http://www.clinicaltrials.gov).

Glucose and insulin administration while maintaining normoglycemia: the GIN concept.

The benefits of tight glucose control in critically ill and surgical patients remains a subject of debate. While some studies demonstrated a survival benefit associated with intensive insulin therapy, more recent studies have failed to demonstrate this correlation. On the contrary, the difficulty in achieving normoglycemia with the conventional insulin sliding scale protocols and a rising concern for severe hypoglycemic episodes associated with this strategy keep many clinicians skeptical. This article examines the use of hyperinsulinemic-normoglycemic clamping, or glucose-insulin-normoglycemia (GIN) therapy, a novel approach to achieve normoglycemia in the perioperative period. If properly applied, this therapy potentially reduces the morbidity and mortality associated with hyperglycemia and confers the pharmacological advantages of hyperinsulinemia. Further understanding of the underlying molecular mechanisms, as well as the development of a continuous intravenous glucose monitoring device would facilitate the routine clinical use of GIN therapy.

Awake videolaryngoscopy-assisted tracheal intubation of the morbidly obese.

Awake videolaryngoscopy may be useful for the tracheal intubation of the morbidly obese. This prospective, observational study enrolled 50 patients undergoing bariatric surgery. After sedation and topical anaesthesia of the airway, awake tracheal intubation was attempted, assisted by videolaryngoscopy, and terminated if there was severe gagging, coughing, or inadequate laryngeal view. After three attempts the procedure was considered a failure. Twenty-seven intubations were successful on the first attempt, fifteen on the second, six on the third and two were not successful, giving a success rate of 96% (95% CI 86-100%). In one failure, inserting the tracheal tube caused severe gagging in spite of an adequate view of the larynx, and the trachea was intubated with the videolaryngoscope after induction of anaesthesia. The second failure was due to gagging, with subsequent tracheal intubation successful using fibreoptic bronchoscopy. When managing the morbidly obese airway, awake tracheal intubation using videolaryngoscopy may be considered.

Jet ventilation for the excision of vocal cord polyps in a pregnant patient.

The anaesthetic management of patients presenting with laryngeal tumours and airway obstruction is difficult. We present the case of a pregnant woman at 30 weeks gestation who underwent surgical removal of two vocal cord polyps under general anaesthesia using jet ventilation

Atomised lidocaine for airway topical anaesthesia in the morbidly obese: 1% compared with 2%.

Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients was evaluated using two doses of local anaesthetic. In this randomised, blinded prospective study, 40 ml of atomised 1% (n = 11) or 2% (n = 10) lidocaine was administered with high oxygen flow as carrier. Outcomes included time for intubation, patient tolerance to airway manipulation, haemodynamic parameters, the bronchoscopist's overall satisfaction, and serial serum lidocaine concentrations. Patients receiving lidocaine 1% had a longer mean (SD) time from the start of topicalisation to tracheal tube cuff inflation than those receiving lidocaine 2% (8.6 (0.9) min vs 6.9 (0.5) min, respectively; p < 0.05). Patients in the 1% cohort demonstrated increased responses to airway manipulation (p < 0.0001), reflecting lower bronchoscopist's satisfaction scores (p < 0.03). Haemodynamic responses to topicalisation and airway manipulation were similar in both groups. Peak plasma concentration was lower in the 1% group (mean (SD) 1.4 (0.3) and 3.8 (0.5) microg.ml(-1), respectively; p < 0.001). Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in the morbidly obese is efficacious, rapid and safe. Compared with lidocaine 1%, the 2% dose provides superior intubating conditions.

Anaesthetic management of parturients with hereditary haemorrhagic telangiectasia for caesarean section.

Hereditary haemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is a vascular disorder characterized by multiple mucocutaneous and visceral arteriovenous malformations. There is little in the literature about the anaesthetic management of parturients with this condition. We report the anaesthetic management for caesarean section of two such parturients. One patient, with significant pulmonary involvement, received neuraxial anaesthesia for caesarean delivery. The second patient had general anaesthesia because investigations could not rule out neurological involvement. We review and discuss the anaesthetic considerations for obstetric patients with hereditary haemorrhagic telangiectasia.

Airway topicalisation in morbidly obese patients using atomised lidocaine: 2% compared with 4%.

We evaluated the technique of airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients using two doses of local anaesthetic. Morbidly obese patients were allocated to receive either 2% or 4% lidocaine (40 ml) for oral airway anaesthesia using an atomiser with high oxygen flow. Patients were carefully sedated using midazolam and fentanyl. Outcomes included patient tolerance to airway manipulation, haemodynamic parameters, and serial plasma lidocaine concentrations. In all, 27 patients were enrolled in the study (2% cohort n = 14, 4% cohort n = 13). Patient characteristics and time for topicalisation and airway management were similar. Haemodynamic parameters did not change significantly. Tolerance to insertion of the Ovassapian airway, bronchoscopy, and tracheal tube positioning was excellent (12 vs 12 patients, 12 vs 12 patients, and 8 vs 12 patients had no response, respectively, 2% vs 4%). Differences did not reach statistical significance. Peak plasma lidocaine concentration was significantly lower in the 2% group (2.8 (0.8) microg.ml(-1) compared with 6.5 (1.0) microg.ml(-1), p < 0.05). Airway anaesthesia using atomised lidocaine for awake fibreoptic intubation in the morbidly obese is efficacious, rapid, and safe. Compared with 4% lidocaine, the 2% dose provides acceptable intubating conditions in most cases and produces lower plasma lidocaine levels.

The management of severe emergence agitation using droperidol.

Emergence agitation can occur following recovery from general anaesthesia. The patient may exhibit aggressive behaviour, disorientation, agitation and restlessness. Untreated, this complication may result in significant morbidity. We report two cases where droperidol was successfully used in the management of severe emergence agitation. In the first case, droperidol was administered to prevent the occurrence of postoperative agitation in a patient known to suffer from this condition following previous general anaesthetics. In the second case, droperidol was used to treat emergence agitation in a morbidly obese patient with a difficult airway who was aggressive and difficult to restrain. Both of these patients remained calm and co-operative, with stable cardio-respiratory parameters, following the administration of droperidol and showed no further signs of agitation. We suggest that droperidol is an effective medication that may be used to prevent and treat severe emergence agitation due to its rapid sedative effect and minimal cardio-respiratory depression.