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.

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.

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.

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.