Positive end-expiratory pressure during laparoscopy: cardiac and respiratory effects

Study ObjectiveTo determine the effect of positive end-expiratory pressure (PEEP) on the respiratory system and on cardiac function.DesignProspective randomized study.SettingOperating room.Patients60 ASA physical status 1 women scheduled for pelvic laparoscopic surgery.InterventionsPatients were ventilated normally during surgery; PEEP was modified depending on patient group allocation. Group A was the control group and did not receive PEEP. Group B received PEEP 5 cmH₂O and Group C received PEEP 10 cmH₂O.MeasurementsRespiratory parameters measured were partial pressure of arterial oxygen (PaO₂), partial pressure of carbon dioxide (PaCO₂), and end-tidal carbon dioxide tension (ETCO₂). Cardiac parameters measured were left ventricular end-diastolic volume index (LVEDVI), ie, ratio of LVEDV/body surface area (BSA; [LVEDVI = end-diastolic volume [EDV]/BSA); left ventricular (LV) systolic function, tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (FAC), RV dimensions in the apical 4-chamber view, tracing basal and mid-cavity minor dimensions and longitudinal dimension, cardiac index, systolic pulmonary artery pressure (PASP), and systolic RV pressure (RVSP). Respiratory and cardiac measurements were recorded at T0 (baseline); T1 (after anesthesia induction, before pneumoperitoneum induction); at 10 (T2), 20 (T3), and 30 (T4) minutes after CO₂ insufflation; and at the end of surgery (T5).Main ResultsVentilation with PEEP at 10 cm H₂O led to significant improvement in both respiratory and cardiac parameters. A reduction in pulmonary vascular resistance and enhanced washout of expiratory CO₂ occurred. Ten and, to a lesser extent, 5 cm H₂O of PEEP decreased LV stroke work.ConclusionsVentilation with PEEP (up to 10 cm H₂O) recruits the hypoventilated areas of the lungs and reduces cardiac afterload.     

Intraocular pressure variation during colorectal laparoscopic surgery: standard pneumoperitoneum leads to reversible elevation in intraocular pressure

Background

The potential effects of laparoscopic surgery on intra- and postoperative intraocular pressure (IOP) are not completely understood. Although prior studies have reported that pneumoperitoneum may increase IOP, it is not clear whether this increase is related to the effects of pneumoperitoneum or to the patient’s position, such as the Trendelenburg position. This study aimed to evaluate the potential fluctuations of IOP during colorectal laparoscopic surgery in two groups of patients: those with and those without Trendelenburg positioning.

Methods

For this prospective study 45- to 85-year-old patients undergoing laparoscopic colorectal surgery were enrolled after a thorough ophthalmologic assessment. The study protocol included measurement of IOP at eight different time points (before, during, and after surgery) using a contact tonometer in both eyes.

Results

The study enrolled 29 patients: 17 (58.6 %) with Trendelenburg position placement during surgery and 12 (41.4 %) without Trendelenburg positioning. The two groups did not differ in terms of gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) class, or operative time. In all the patients, pneumoperitoneum induction led to a mild rise in IOP, averaging 4.1 mmHg. The patients with Trendelenburg positioning showed a greater increase than the patients without it (5.05 vs 4.23 mmHg at 45 min; p = 0.179), but IOP evaluation 48 h after surgery showed no substantial differences between the two groups. Among the 29 patients, 17 (58.6 %) showed an increase in IOP of 5 mmHg or more during surgery. A greater percentage of the patients who underwent Trendelenburg positioning showed an IOP increase of 5 mmHg or more (76.5 vs 33.3 %; p = 0.020). At the multivariate analysis, no potential predictors of increased IOP during surgery was identified.

Conclusions

Standard pneumoperitoneum (≤14 mmHg) led to mild and reversible IOP increases. A trend was observed toward a greater IOP increase in patients with Trendelenburg positioning. Thus, the patient’s position during surgery may represent a stronger risk factor for IOP increase than pneumoperitoneum-related intraabdominal pressure.     

Microglial polarization and plasticity: Evidence from organotypic hippocampal slice cultures

Increasing evidence indicates that “functional plasticity” is not solely a neuronal attribute but a hallmark of microglial cells, the main brain resident macrophage population. Far from being a univocal phenomenon, microglial activation can originate a plethora of functional phenotypes, encompassing the classic M1 proinflammatory and the alternative M2 anti‐inflammatory phenotypes. This concept overturns the popular view of microglial activation as a synonym of neurotoxicity and neurogenesis failure in brain disorders. The characterization of the alternative programs is a matter of intense investigation, but still scarce information is available on the course of microglial activation, on the reversibility of the different commitments and on the capability of preserving molecular memory of previous priming stimuli. By using organotypic hippocampal slice cultures as a model, we developed paradigms of stimulation aimed at shedding light on some of these aspects. We show that persistent stimulation of TLR4 signaling promotes an anti‐inflammatory response and microglial polarization toward M2‐like phenotype. Moreover, acute and chronic preconditioning regimens permanently affect the capability to respond to a later challenge, suggesting the onset of mechanisms of molecular memory. Similar phenomena could occur in the intact brain and differently affect the vulnerability of mature and newborn neurons to noxious signals. GLIA 2013;61:1698–1711     

Cross-sex hormone administration changes pain in transsexual women and men

Chronic pain is gender-related, since there is a clear predominance of one sex with respect to the other in most pain syndromes. Gonadal hormones are known to affect the occurrence and incidence of pain. Transsexuals receive cross-sex hormones to develop and maintain somatic characteristics of the opposite sex: male to female transsexuals (MtF) are administered estrogens and anti-androgens, while female to male transsexuals (FtM) are administered androgens. Hence, these subjects represent a model to study the relationship between sex hormones and pain. Questionnaires dealing with sociodemographic data and pain (occurrence, frequency, duration, intensity, location and associated symptoms) were administered to both MtF and FtM transsexuals under hormone treatment for sex reassignment for at least 1 year. Forty-seven MtF and 26 FtM completed the questionnaires. Fourteen of the 47 MtF (29.8%) reported painful conditions, which in 11 subjects were not present before the beginning of hormone treatment. Pain consisted mainly of headaches and breast and musculoskeletal pain. Five subjects suffered from more than one pain condition. Sixteen of the 26 FtM (61.5%) reported pain. In 11 subjects, the pain was present before the beginning of hormone intake, and in 6 of them it improved after testosterone administration. These data suggest that marked changes in sex hormones affect the occurrence of pain in a high percentage of humans but not in all of them. Whether these effects are due to peripheral or central actions of sex steroids is unknown.     

ITPA Activity in Children Treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and Inflammatory Response

Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological diseases such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reactions (ADRs) and drug response is observed. This study investigated (i) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, and (ii) the relationship between ITPA activity and the inflammatory activity observed in children with IBD. ITPA and TPMT activities were determined in 106 children with immunological disease on AZA therapy. Markers of hepatotoxicity, myelotoxicity, pancreatitis and inflammation as well as clinical information were retrospectively collected during regular medical visits. No significant association was found between ITPA activity and hepatotoxicity or clinical ADRs such as cutaneous reactions, arthralgia, flulike symptoms and gastrointestinal disorders. Concerning myelotoxicity, a significant relation was observed between ITPA activity and RBC mean corpuscular volume (MCV; p=0.003). This observation may be related to the significant relationship found between high ITPA activity and the increase in γ‐globulin level reflecting inflammation (p=0.005). In our study, ITPA activity was not associated with occurrence of ADRs, but a relationship between high ITPA activity and γ‐globulin, a marker of inflammation, was found in children with IBD. Therefore, measurement of ITPA activity may help to identify children with IBD predisposed to residual inflammation on AZA therapy. Further prospective studies are needed to confirm this result.     

Do Patients Who Participate in a Clinic Experimental Protocol Have the Same Probability of Success From That Who Were Not Selected or Refused To Participate? Outcome Surveillance,Safety, and Bioethical Considerations in Kidney Transplant Clinical Research

Introduction

Safety in conducting a clinical trial is a prerequisite for patients who will be enrolled into that study. The aim of the present study was to evaluate retrospectively if patient and graft survival were similar among patients who participated in clinical trials versus those who did not.

Patients and Methods

We evaluated pretransplant and posttransplant characteristics of 245 kidney transplant (KT) patients who were selected to participate in at least one Phase II/Phase III clinical trial. We compared them with 361 KT patients who were not enrolled or refused to participate in those clinical trials; all studies were conducted at a single transplant center. Inclusion/exclusion criteria were as noted for each individual protocol. Only studies with enrollment at time of graft implant were considered.

Results

Selection of patients participating in clinical trials in general exclude high-risk patients. In our experience, only 36% of transplanted patients were selected for a multicenter, prospective, randomized, international study that included changes to the strategies in the administration of immunosuppressive drugs already on the market or development of a new immunosuppressant. After 5 years, graft and patient survival rates were similar between those who participated and those who did not participate in a clinical study. Although our data were collected retrospectively, an alternative design to achieve these conclusions would be a noninferiority study.

Conclusions

Our results demonstrated similar rates of graft and patient survival among enrolled patients versus nonenrolled patients. Outcome surveillance offers safety in participating in clinical trials that involve changes in standard immunosuppression therapy and are part of the research necessary to develop patient-centered medical interventions.     

Desferioxamine increases iron depletion and apoptosis induced by ara-C of human myeloid leukaemic cells

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 n M ara-C for 48 h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.