Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions.

Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.

Development of objective performance metrics for ultrasound-guided internal jugular vein cannulation on behalf of the College of Anaesthesiologists of Ireland and observation of scores amongst novice and experienced operators.

BACKGROUND: Ultrasound-guided, internal jugular venous (IJV) cannulation is a core technical skill for anaesthesiologists and intensivists. OBJECTIVES: At a modified Delphi panel meeting, to define and reach consensus on a set of objective ultrasound-guided IJV cannulation performance metrics on behalf of the College of Anaesthesiologists of Ireland (CAI). To use these metrics to objectively score video recordings of novice and experienced anaesthesiologists. DESIGN: An observational study. SETTING: CAI, March to June 2016 and four CAI training hospitals, November 2016 to July 2019. PARTICIPANTS: Metric development group: two CAI national directors of postgraduate training (specialist anaesthesiolgists), a behavioural scientist, a specialist intensivist and a senior CAI trainee. Scoring by two blinded assessors of video recordings of novice ( n  = 11) and experienced anaesthesiologists ( n  = 15) ultrasound-guided IJV cannulations. MAIN OUTCOME MEASURES: A set of agreed CAI objective performance metrics, that is, steps, errors, and critical errors characterising ultrasound-guided IJV cannulation. The difference in performance scores between novice and experienced anaesthesiologists as determined by skill level defined as being below or above the median total error score (errors plus critical errors): that is, low error (LoErr) and high error (HiErr), respectively. RESULTS: The study identified 47 steps, 18 errors and 13 critical errors through six phases.Variability was observed in the range of total error scores for both novice (1 to 3) and experienced (0 to 4.5) anaesthesiologists. This resulted in two further statistically different subgroups (LoErr and HiErr) for both novice ( P  = 0.011) and experienced practitioners ( P  < 0.000). The LoErr-experienced group performed the best in relation to steps, errors and total errors. Critical errors were only observed in the experienced group. CONCLUSION: A set of valid, reliable objective performance metrics has been developed for ultrasound-guided IJV cannulation. Considerable skill variability underlines the need to develop a CAI simulation-training programme using these metrics.

Efficacy of a Laparoscopically Delivered Transversus Abdominis Plane Block Technique during Elective Laparoscopic Cholecystectomy: A Prospective, Double-Blind Randomized Trial.

BACKGROUND: The management of postoperative pain is paramount to facilitate the delivery of day case surgical programs. In recent years, the complexity of procedures carried out has increased to include laparoscopic cholecystectomy. The aim of this study was to evaluate the impact of laparoscopic-assisted 4-quadrant transversus abdominis plane (TAP) block vs periportal local anesthetic wound infiltration in managing postoperative pain. STUDY DESIGN: A prospective, randomized, double-blinded trial was conducted with patients undergoing elective laparoscopic cholecystectomy. Patients were randomized using computerized "random number table" into a test group that received laparoscopic-assisted TAP block with bupivacaine with periportal saline injection and a control group that received a laparoscopic-assisted TAP block with saline and periportal bupivacaine. All patients received intraperitoneal instillation of bupivacaine in the gallbladder bed. Postoperative pain scores were recorded using numerical rating scores at rest and coughing at dedicated time points. Statistical analysis was carried out using GraphPad Prism software, version 5 (GraphPad Software) and p < 0.05 was considered significant. RESULTS: Eighty patients (70 female and 10 male) were enrolled; 40 patients were randomized to each group. Age, American Society of Anesthesiologists score, operative time, and BMI were comparable between the groups. No adverse events were encountered with the administration of TAP blocks. Numerical rating scores were significantly reduced in the test group at 1, 3, and 6 hours at rest (p = 0.025, p = 0.03, and p = 0.007, respectively). Numerical rating score was significantly reduced at 1, 3, and 6 hours during coughing (p = 0.026, p = 0.02, and p = 0.03, respectively). Difference in postoperative analgesic requirements between both groups was statistically insignificant (p = 0.17). CONCLUSIONS: This analysis has confirmed the therapeutic benefit of laparoscopically delivered TAP blocks in elective laparoscopic cholecystectomy.

Perioperative modifications of respiratory function.

Postoperative pulmonary complications contribute considerably to morbidity and mortality, especially after major thoracic or abdominal surgery. Clinically relevant pulmonary complications include the exacerbation of underlying chronic lung disease, bronchospasm, atelectasis, pneumonia and respiratory failure with prolonged mechanical ventilation. Risk factors for postoperative pulmonary complications include patient-related risk factors (e.g., chronic obstructive pulmonary disease (COPD), tobacco smoking and increasing age) as well as procedure-related risk factors (e.g., site of surgery, duration of surgery and general vs. regional anaesthesia). Careful history taking and a thorough physical examination may be the most sensitive ways to identify at-risk patients. Pulmonary function tests are not suitable as a general screen to assess risk of postoperative pulmonary complications. Strategies to reduce the risk of postoperative pulmonary complications include smoking cessation, inspiratory muscle training, optimising nutritional status and intra-operative strategies. Postoperative care should include lung expansion manoeuvres and adequate pain control.

Atelectasis in the perioperative patient.

PURPOSE OF REVIEW: To report the impact of atelectasis on perioperative outcomes. Atelectasis occurs in the dependent parts of the lungs of most patients who are anesthetized. Development of atelectasis is associated with decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance and development of lung injury. Here, we examine the etiology, contributing factors, consequences, diagnosis and treatment of atelectasis. RECENT FINDINGS: Atelectasis describes the state of absent air in alveoli attributable to collapse, but recent findings suggest that alveoli are filled with foam and fluid. It is now known that atelectasis plays an important role beyond abnormal gas exchange and that prevention or reversal of atelectasis in some populations of postoperative patients may improve outcome. SUMMARY: Atelectasis in the presence of preexisting lung disease or limited cardiopulmonary reserve may have significant consequences. Increasing understanding of the underlying nature of atelectasis and its contribution to acute lung injury will improve our approach to the prevention and management of atelectasis.

Pulmonary atelectasis: a pathogenic perioperative entity.

Atelectasis occurs in the dependent parts of the lungs of most patients who are anesthetized. Development of atelectasis is associated with decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury. The adverse effects of atelectasis persist into the postoperative period and can impact patient recovery. This review article focuses on the causes, nature, and diagnosis of atelectasis. The authors discuss the effects and implications of atelectasis in the perioperative period and illustrate how preventive measures may impact outcome. In addition, they examine the impact of atelectasis and its prevention in acute lung injury.

Oxygen attenuates atelectasis-induced injury in the in vivo rat lung.

BACKGROUND: Atelectasis results in impaired compliance and gas exchange and, in extreme cases, increased microvascular permeability, pulmonary hypertension, and right ventricular dysfunction. It is not known whether such atelectasis-induced lung injury is due to the direct mechanical effects of lung volume reduction and alveolar collapse or due to the associated regional lung hypoxia. The authors hypothesized that addition of supplemental oxygen to an atelectasis-prone ventilation strategy would attenuate the pulmonary vascular effects and reduce the local levels of vasoconstrictor eicosanoids. METHODS: In series 1, anesthetized, atelectasis-prone mechanically ventilated rats were randomly assigned to one of six groups based on the inspired oxygen concentration and ventilated without recruitment. Series 2 was performed to determine the cardiac and pulmonary vascular effects of 21% versus 100% inspired oxygen. In series 3, computed tomography scans were performed after ventilation with a recruitment strategy (21% O2) or no recruitment strategy (21% O2 or 100% O2). In series 4, functional residual capacity was measured in animals where the gas was 21% or 100% O2. RESULTS: The partial pressure of arterial oxygen increased with increasing inspired oxygen, but the alveolar-arterial oxygenation gradient was also greater with higher inspired oxygen. Ventilation with 21% O2 (but not with 100% O2) was associated with progressive pulmonary vascular impedance and increased pulmonary vascular permeability. Prostaglandin F2alpha was increased by mechanical ventilation, especially without supplemental oxygen. Computed tomography scans demonstrated no atelectasis in recruited lungs, and atelectasis in nonrecruited lungs that was greater with supplemental oxygen. Increased atelectasis with 100% O2 (vs. 21% O2) was demonstrated by measurement of functional residual capacity. CONCLUSIONS: Although supplemental oxygen worsened atelectasis in this model, it prevented the pathologic effects of atelectasis, including microvascular leak and pulmonary hypertension. Atelectasis-induced lung injury seems to be mediated by hypoxia rather than by the direct mechanical effects of atelectasis.

Hypocapnia attenuates mesenteric ischemia-reperfusion injury in a rat model.

PURPOSE: Hypocapnia, a recognized complication of high frequency oscillation ventilation, has multiple adverse effects on lung and brain physiology in vivo, including potentiation of free radical injury. We hypothesized that hypocapnia would potentiate the effects of mesenteric ischemia-reperfusion on bowel, liver and lung injury. METHODS: Anesthetized male Sprague-Dawley rats were ventilated with high frequency oscillation and were randomized to one of four groups, exposed to either mesenteric ischemia-reperfusion or sham surgery, and to either hypocapnia or normocapnia. RESULTS: All animals survived the protocol. Ischemia-reperfusion caused significant histologic bowel injury. Bowel 8-isoprostane generation was greater in ischemia-reperfusion vs sham, but was attenuated by hypocapnia. Laser-Doppler flow studies of bowel perfusion confirmed that hypocapnia attenuated reperfusion following ischemia. Plasma alanine transaminase, reflecting overall hepatocellular injury, was not increased by ischemia-reperfusion but was increased by hypocapnia; however, hepatic isoprostane generation was increased by ischemia-reperfusion, and not by hypocapnia. Oxygenation was comparable in all groups, and compliance was impaired by ischemia-reperfusion but not by hypocapnia. CONCLUSION: Hypocapnia, although directly injurious to the liver, attenuates ischemia-reperfusion induced lipid peroxidation in the bowel, possibly through attenuation of blood flow during reperfusion.

Facial nerve palsy: a complication following anaesthesia in a child with Treacher Collins syndrome.

We report a case of facial nerve palsy following anaesthesia in a child with Treacher Collins syndrome. Children in whom intubation is difficult may be at increased risk of this complication.

Laryngeal mask cuff inflation at removal does not affect early postoperative laryngopharyngeal morbidity.

PURPOSE: We assessed the effect of cuff inflation of the laryngeal mask airway at removal on sore throat, pharyngeal morbidity and airway complications. METHODS: In a prospective randomized trial, we used a standardized technique of anesthesia and of laryngeal mask insertion in 126 consecutive day-case patients. Postoperatively, on eye opening, the masks were removed either inflated (Group A) or deflated (Group B) and examined for blood by a blinded observer. Episodes of coughing, gagging, laryngospasm, hiccups and retching, and symptoms of sore throat and hoarseness were recorded by the same observer. RESULTS: Demographics were similar. Bloodstaining occurred in 21% of patients in Group A (n = 63) vs 13% in Group B (n = 63; P = 0.23); the incidence of sore throat was identical (19%). Group A experienced more hoarseness (22% vs 9%; P = 0.05). Overall airway complications did not differ between groups (19% vs 11%; P = 0.21). CONCLUSION: We conclude that removal of the laryngeal mask airway inflated does not reduce the incidence of sore throat, pharyngeal morbidity or airway complications.

Benzodiazepine premedication may attenuate the stress response in daycase anesthesia: a pilot study.

PURPOSE: Patients undergoing daycase surgery suffer from varying degrees of fear and anxiety. There is conflicting evidence in the literature regarding the benefit of benzodiazepine premedication in daycase surgery. We carried out a prospective, double-blind, randomized pilot study investigating the effect of benzodiazepine premedication on the stress response in patients undergoing daycase anesthesia and surgery. METHODS: Group I (n = 16) received diazepam 0.1 mg*kg(-1) orally 60 min preoperatively; Group II (n = 15) received diazepam 0.1 mg*kg(-1) orally 90 min preoperatively; Group III (n = 30) received a placebo. The stress response was measured by analyzing urinary catecholamine and cortisol levels and by scoring anxiety levels using state-trait anxiety inventory (STAI) scores and visual analogue scores (VAS). RESULTS: Anxiety scores (VAS and STAI scores) were not different between groups. We found a statistically significant reduction in urinary cortisol and noradrenaline levels in the groups receiving diazepam vs placebo. DISCUSSION: The reduction in stress hormones following diazepam premedication, in patients undergoing daycase surgery may support the role for benzodiazepine premedication in this setting. However, further studies are warranted to determine the clinical significance of these findings.

Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation.

OBJECTIVE: Deliberate elevation of PaCO2 (therapeutic hypercapnia) protects against lung injury induced by lung reperfusion and severe lung stretch. Conversely, hypocapnic alkalosis causes lung injury and worsens lung reperfusion injury. Alterations in lung surfactant may contribute to ventilator-associated lung injury. The potential for CO2 to contribute to the pathogenesis of ventilator-associated lung injury at clinically relevant tidal volumes is unknown. We hypothesized that: 1) hypocapnia would worsen ventilator-associated lung injury, 2) therapeutic hypercapnia would attenuate ventilator-associated lung injury; and 3) the mechanisms of impaired compliance would be via alteration of surfactant biochemistry. DESIGN: Randomized, prospective animal study. SETTING: Research laboratory of university-affiliated hospital. SUBJECTS: Anesthetized, male New Zealand Rabbits. INTERVENTIONS: All animals received the same ventilation strategy (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O; rate, 42 breaths/min) and were randomized to receive FiCO2 of 0.00, 0.05, or 0.12 to produce hypocapnia, normocapnia, and hypercapnia, respectively. MEASUREMENTS AND MAIN RESULTS: Alveolar-arterial oxygen gradient was significantly lower with therapeutic hypercapnia, and peak airway pressure was significantly higher with hypocapnic alkalosis. However, neither static lung compliance nor surfactant chemistry (total surfactant, aggregates, or composition) differed among the groups. CONCLUSIONS: At clinically relevant tidal volume, CO2 modulates key physiologic indices of lung injury, including alveolar-arterial oxygen gradient and airway pressure, indicating a potential role in the pathogenesis of ventilator-associated lung injury. These effects are surfactant independent.

Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs.

During mechanical ventilation, lung recruitment attenuates injury caused by high VT, improves oxygenation, and may optimize pulmonary vascular resistance (PVR). We hypothesized that ventilation without recruitment would induce injury in otherwise healthy lungs. Anesthetized rats were ventilated with conventional mechanical ventilation (VT 8 ml/kg; respiratory frequency 40 per minute) and 21% inspired oxygen, with or without a recruitment strategy consisting of recruitment maneuvers plus positive end-expiratory pressure, in the presence or absence of a laparotomy. Additional experiments examined the impact of atelectasis on right ventricular function using echocardiography, as well as functional residual capacity and PVR. Lack of recruitment resulted in reduced overall survival (59% nonrecruited vs. 100% recruited, p < 0.05), increased microvascular leak, greater impairment of oxygenation and lung compliance, increased PVR, and elevated plasma lactate. Echocardiography demonstrated that right ventricular dysfunction occurred in the absence of recruitment. Finally, samples from nonrecruited lungs demonstrated ultrastructural evidence of microvascular endothelial disruption. Although such effects clearly do not occur with comparable magnitude in the clinical context, the current data suggest novel mechanisms (microvascular leak, right ventricular dysfunction) whereby derecruitment may contribute to development of lung injury and adverse systemic outcome.