A prospective randomized clinical trial to evaluate the impact of intraoperative ventilation with high oxygen content on the extent of postoperative pneumocephalus in patients undergoing craniotomies.

Purpose of the article: To determine whether intraoperative ventilation with pure oxygen during the last stage of surgery reduces the occurrence and volume of postoperative pneumocephalus when compared to conventional air/oxygen mixture in patients undergoing craniotomy. MATERIAL AND METHODS: prospective randomized single-blinded study to compare the rate of occurrence and volume of postoperative pneumocephalus in patients undergoing craniotomy receiving intraoperative ventilation with pure oxygen (Group B) versus a conventional air/oxygen 1:1 mixture (Group A) during the last stage of surgery. This trial was registered in ClinicalTrials.gov #NCT02722928, protocol number 2015H0032. RESULTS: One hundred patients were randomized into group 'A' and group 'B'. Seventy patients were included in the final analysis with 39 patients allocated in group 'A' and 31 patients in group 'B'. Median and IQR were used for postoperative penumocephalus volume. Group A: 9.65 [3.61-23.20]; Group B: 7.06 [2.70-20.1]. Our study showed no prophylactic effect on postoperative pneumocephalus volume when using mechanical ventilation with higher oxygen concentrations than the standard FiO2 during the last stage of surgery in patients undergoing craniotomy (p = .47). No statistical difference was found in SICU LOS between groups (median 1,380 min [group A] versus 1,524 min [group B]; p = .18). CONCLUSION: The use of intraoperative mechanical ventilation with pure oxygen was not associated with a prophylactic effect on the occurrence and extent of postoperative pneumocephalus in our patient setting. Published literature describing the extent of postoperative pneumocephalus is limited or highly variable among institutions.

PONV management in patients with QTc prolongation on the EKG.

Postoperative nausea and vomiting (PONV) is a commonly encountered problem in surgical practice. It delays discharge from the post-anesthesia care unit, requires additional resources to treat, and may increase the morbidity in some patients. Many effective drugs are available to treat or prevent PONV, however many of these drugs have the potential to prolong the QTc on the electrocardiogram (EKG) and increase the risk of serious ventricular arrhythmias, in particular, torsade de pointes. The QTc prolongation may be a manifestation of a genetic mutation resulting in abnormal myocyte repolarization or it may be acquired and associated with the use of various medications, electrolyte disorders, and physiological conditions. Patients predisposed to QTc prolongation presenting for surgery constitute a challenging group, since many drugs commonly used for PONV management will put them at risk for perioperative serious arrhythmias. This is an important topic, and our mini-review is an attempt to highlight the problem, summarize the existing experience, and generate recommendations for safe management of PONV for patients, who are at increased risk of QTc prolongation and arrhythmias. Focused prospective studies will help to find definitive answers to the discussed problems and challenges and develop specific guidelines for clinical application.

Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small molecular tracer and positron emission tomography.

Positron emission tomography (PET) with epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide the means for noninvasive and repetitive imaging of heterogeneity of EGFR expression and signaling activity in tumors in individual patients before and during therapy with EGFR signaling inhibitors. We developed the synthesis and (124)I-radiolabeling of the (E)-But-2-enedioic acid [4-(3-[(124)I]iodoanilino)-quinazolin-6-yl]-amide-(3-morpholin-4-yl-propyl)-amide (morpholino-[(124)I]-IPQA), which selectively, irreversibly, and covalently binds the adenosine-triphosphate-binding site to the activated (phosphorylated) EGFR kinase, but not to the inactive EGFR kinase. The latter was demonstrated using in silico modeling with crystal structures of the wild type and different gain-of-function mutants of EGFR kinases. Also, this was demonstrated by selective radiolabeling of the EGFR kinase domain with morpholino-[(131)I]-IPQA in A431 human epidermoid carcinoma cells and Western blot autoradiography. In vitro radiotracer accumulation and washout studies demonstrated a rapid accumulation and progressive retention postwashout of morpholino-[(131)I]-IPQA in A431 epidermoid carcinoma and in U87 human glioma cells genetically modified to express the EGFRvIII mutant receptor, but not in the wild-type U87MG glioma cells under serum-starved conditions. Using morpholino-[(124)I]-IPQA, we obtained noninvasive PET images of EGFR activity in A431 subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown from K562 human chronic myeloid leukemia cells in immunocompromised rats and mice. Based on these observations, we suggest that PET imaging with morpholino-[(124)I]-IPQA should allow for identification of tumors with high EGFR kinase signaling activity, including brain tumors expressing EGFRvIII mutants and nonsmall-cell lung cancer expressing gain-of-function EGFR kinase mutants. Because of significant hepatobiliary clearance and intestinal reuptake of the morpholino-[(124)I]-IPQA, additional [(124)I]-IPQA derivatives with improved water solubility may be required to optimize the pharmacokinetics of this class of molecular imaging agents.