Tom Schepens

Considerable exposure to the endocrine disrupting chemicals phthalates and bisphenol-A in intensive care unit (ICU) patients.

Critical care medicine has largely benefited from plastic-containing medical devices. However, bisphenol-A (BPA) and phthalates present in the plastics can leach from such devices. We hypothesized that intensive care unit (ICU) patients are exposed to BPA and phthalates through (plastic) medical devices. Serum (n = 118) and urine (n= 102) samples of adult ICU patients (n = 35) were analyzed for total BPA and phthalate metabolites (PMs). Our results showed that adult ICU patients are continuously exposed to phthalates, such as di(2-ethylhexyl)phthalate (DEHP), as well as to BPA, albeit to a lesser extent. This exposure resulted in detectable high serum and urinary levels in almost every patient and at every studied time point. Moreover, these levels were significantly higher than in controls or compared to referenced literature. The chronology of exposure was demonstrated: pre-operative urinary and serum levels of the DEHP metabolites were often below the detection limit. Plastic-containing medical devices were the main source of DEHP exposure: post-operative patients on hemofiltration, extracorporeal membrane oxygenation or both showed serum levels 100-or 1000-fold higher than the levels in the general population reported in the literature. The serum and some of the urinary levels of the DEHP metabolites are the highest ever reported in humans; some at biologically highly relevant concentrations of ≥ 10-50 μM. Despite the continuously tightening regulations, BPA and DEHP appear to be still present in (some) medical devices. Because patient safety is a concern in the ICU, further research into the (possibly toxic and clinical) effects of these chemicals released from medical devices is imperiously necessary.

Is acyclovir effective among critically ill patients with herpes simplex in the respiratory tract

BACKGROUND AND OBJECTIVE The relevance of the detection of herpes simplex virus type 1 (HSV-1) in the respiratory tract of patients in the intensive care unit (ICU) is unclear. Therefore, it is uncertain whether treatment with an antiviral agent could be beneficial for these patients. STUDY DESIGN We retrospectively reviewed the records of ICU patients with a positive HSV-1 culture in the respiratory tract or bronchoalveolar lavage (BAL) fluid. We evaluated whether acyclovir treatment (n=106) could have a beneficial effect on mortality as compared with the standard treatment (n=106). RESULTS Acyclovir treatment was positively linked to in-hospital and ICU-mortality reduction. This favourable influence remained present after correcting for possible confounders and using propensity-adjusted and propensity-matched cohorts: with an odds ratio in the treated group of 3.19 (95% CI 1.79-5.69, p=0.001) for ICU survival and of 3.55 (95% CI 2.16-5.85, p<0.001) for in-hospital survival. The subgroup with HSV-1 detected in the BAL-fluid is the sole contributor to this difference. In the BAL-fluid detected group, 48% (n=10) of non-treated patients died in the ICU, versus 21% (n=6) in the acyclovir-treated group (p=0.033), occurring despite an even longer duration of ventilation or ICU stay. CONCLUSIONS These data highlight the hypothesis that it might be worthwhile to consider treatment of HSV-1 in ICU patients depending on the type of respiratory sample in which the virus is detected. These results warrant a prospective trial to prove causality.

The endotracheal tube microbiome associated with Pseudomonas aeruginosa or Staphylococcus epidermidis

Ventilator-associated pneumonia (VAP) is one of the commonest hospital-acquired infections associated with high mortality. VAP pathogenesis is closely linked to organisms colonizing the endotracheal tube (ETT) such as Staphylococcus epidermidis and Pseudomonas aeruginosa, the former a common commensal with pathogenic potential and the latter a known VAP pathogen. However, recent gut microbiome studies show that pathogens rarely function alone. Hence, we determined the ETT microbial consortium co-colonizing with S. epidermidis or P. aeruginosa to understand its importance in the development of VAP and for patient prognosis. Using bacterial 16S rRNA and fungal ITS-II sequencing on ETT biomass showing presence of P. aeruginosa and/or S. epidermidis on culture, we found that presence of P. aeruginosa correlated inversely with patient survival and with bacterial species diversity. A decision tree, using 16S rRNA and patient parameters, to predict patient survival was generated. Patients with a relative abundance of Pseudomonadaceae <4.6% and of Staphylococcaceae <70.8% had the highest chance of survival. When Pseudomonadaceae were >4.6%, age of patient <66.5 years was the most important predictor of patient survival. These data indicate that the composition of the ETT microbiome correlates with patient prognosis, and presence of P. aeruginosa is an important predictor of patient outcome.

Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers.

BACKGROUND The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. OBJECTIVE To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. DESIGN A randomised, controlled, parallel-group, single-centre, double-blinded study. SETTING District general hospital in Belgium. PARTICIPANTS Twelve healthy male volunteers. INTERVENTIONS Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg−1, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg−1 (n = 6) or neostigmine 70 &mgr;g kg−1 (n = 6). MAIN OUTCOME MEASURES EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. RESULTS During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) &mgr;V in the neostigmine group and 1.6 (1.3 to 1.9) &mgr;V in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 &mgr;V vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). CONCLUSION EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. TRIAL REGISTRATION EudraCT ref: 2013-002078-30.

Diaphragmatic and intercostal electromyographic activity during neostigmine, sugammadex and neostigmine-sugammadex-enhanced recovery after neuromuscular blockade: A randomised controlled volunteer study.

BACKGROUND Electromyographic activity of the diaphragm (EMGdi) during weaning from mechanical ventilation is increased after sugammadex compared with neostigmine. OBJECTIVE To determine the effect of neostigmine on EMGdi and surface EMG (sEMG) of the intercostal muscles during antagonism of rocuronium block with neostigmine, sugammadex and neostigmine followed by sugammadex. DESIGN Randomised, controlled, double-blind study. SETTING Intensive care research unit. PARTICIPANTS Eighteen male volunteers. INTERVENTIONS A transoesophageal EMGdi recorder was inserted into three groups of six anaesthetised study participants, and sEMG was recorded on their intercostal muscles. To reverse rocuronium, volunteers received 50 &mgr;g kg−1 neostigmine, 2 mg kg−1 sugammadex or 50 &mgr;g kg−1 neostigmine, followed 3 min later by 2 mg kg−1 sugammadex. MAIN OUTCOME MEASURES We examined the EMGdi and sEMG at the intercostal muscles during recovery enhanced by neostigmine or sugammadex or neostigmine–sugammadex as primary outcomes. Secondary objectives were the tidal volume, PaO2 recorded between the onset of spontaneous breathing and extubation of the trachea and SpO2 during and after anaesthesia. RESULTS During weaning, median peak EMGdi was 0.76 (95% confidence interval: 1.20 to 1.80) &mgr;V in the neostigmine group, 1.00 (1.23 to 1.82) &mgr;V in the sugammadex group and 0.70 (0.91 to 1.21) &mgr;V in the neostigmine–sugammadex group (P < 0.0001 with EMGdi increased after sugammadex vs. neostigmine and neostigmine–sugammadex). The median peak intercostal sEMG for the neostigmine group was 0.39 (0.65 to 0.93) &mgr;V vs. 0.77 (1.15 to 1.51) &mgr;V in the sugammadex group and 0.82 (1.28 to 2.38) &mgr;V in the neostigmine–sugammadex group (P < 0.0001 with sEMG higher after sugammadex and after neostigmine–sugammadex vs. neostigmine). CONCLUSION EMGdi and sEMG on the intercostal muscles were increased after sugammadex alone compared with neostigmine. Adding sugammadex after neostigmine reduced the EMGdi compared with sugammadex alone. Unlike the diaphragm, intercostal EMG was preserved with neostigmine followed by sugammadex. TRIAL REGISTRATION EudraCT: 2015-001278-16; ClinicalTrials.gov: NCT02403063.

Predictors of Insulin Resistance in Obesity and Type 2 Diabetes Mellitus - The Role of Magnesium

Objectives: Hypomagnesaemia and insulin resistance are two major clinical problems, with intertwining pathophysiology. We aimed to explore this association in obese patients and in non-insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods: Subjects were recruited from the outpatient diabetes/obesity clinic of the Antwerp University Hospital. The population (N=2731) consists of 2 subject groups with different degrees of insulin resistance and insulin secretory potential: 1) overweight (Body Mass index (BMI) ≥ 25 kg/m² and <30 kg/m²) and obese (BMI ≥ 30 kg/m²) subjects, 2) adult T2DM patients. Hypomagnesaemia was defined as serum magnesium <1.7 mg/dl. Insulin resistance was estimated using the Homeostasis model assessment (HOMA-IR; cut-off point 2.82). Results: Hypomagnesaemia was present in 6.1% of the entire population. Patients with hypomagnesaemia had more visceral adipose tissue (VAT), and a higher HOMA-IR. They suffered more from the metabolic syndrome and T2DM. Patients with a HOMA-IR<2.82 were younger, had lower BMI and less VAT. They suffered less from hypomagnesaemia. Hypomagnesaemia was more prevalent in T2DM patients than in obese subjects without T2DM. Although serum magnesium and HOMA-IR were negatively correlated, logistic regression analysis showed that magnesium was not a significant predictor for HOMA-IR. Conclusions: Despite a significant negative correlation between magnesium and HOMA-IR, magnesium was not retained as a significant determinant of insulin resistance compared to the other predictors in our population of obese subjects and T2DM patients.

Red cell distribution width (RDW) as a biomarker for respiratory failure in a pediatric ICU

BackgroundThe red cell distribution width (RDW) is a widely available, inexpensive, and highly reproducible test that reflects the range of the red cell sizes. Any process that releases reticulocytes in the circulation will result in an increase in RDW. Elevated RDW values are linked to worsened pulmonary function in the adult population. We performed a retrospective cohort study to describe the association between RDW and respiratory failure in critically ill children in a in a pediatric intensive care unit (PICU) in a tertiary university hospital.SubjectsAll patients admitted between January 2009 and June 2015 were considered eligible for inclusion.MethodsRetrospective cohort study.ResultsIn total, 960 patients were included in the cohort analysis. Of those patients, 149 (15.5%) had elevated RDW values. RDW on admission was associated with lower 28 day ventilator-free days. The highest quintile of RDW was associated with the need for mechanical ventilation, even when correcting for anaemia, age and Pediatric Risk of Mortality (PRISM) scores. In the subgroup of ventilated patients, RDW was associated with nadir PaO2/FiO2(P/F) ratios.ConclusionThe RDW value on admission of our PICU patients is associated with a greater need for invasive mechanical ventilation, lower 28 day ventilator-free days and lower nadir P/F ratios in the patients with highest RDW values on admission. RDW may be a valuable, cheap and universally available, prognostic parameter for respiratory dysfunction in the PICU.

Rapid Ventricular Pacing for Neurovascular Surgery: A Study on Cardiac and Cerebral Effects

BACKGROUND AND OBJECTIVE Intraoperative rupture of a cerebral aneurysm during neurosurgery can be a devastating event that increases perioperative morbidity and mortality. Rapid ventricular pacing (RVP) is a technique to obtain flow arrest for short periods of time during dissection or rupture of the aneurysm. The objective of this study was to evaluate the neurological and cardiac effects of repetitive periods of RVP during cerebrovascular surgery. METHODS Data from patients who underwent repetitive RVP during craniotomy for cerebrovascular disorders were retrospectively analyzed from a single-center medical records database (Cegeka Medical Health Care Systems). We compared preoperative and postoperative troponin levels (cTnI) to assess cardiac ischemia. Preoperative and postoperative magnetic resonance imaging (MRI) results were screened for RVP-induced infarcts by evaluating diffusion restriction in the hemisphere contralateral to the operated side and the fossa posterior. RESULTS A total of 37 patients were analyzed. An immediate decrease of systolic arterial blood pressure (<60 mm Hg) was achieved after initiation of RVP. Postoperative MRI did not reveal areas of diffusion restriction. RVP tended to be a predictor of postoperative cTnI increase. Preoperative and postoperative cTnI levels were higher in patients with a subarachnoid hemorrhage compared to patients without one. After 24 hours cTnI jevels normalized to preoperative values. CONCLUSIONS Systolic arterial blood pressure decreased after RVP but normalized immediately when pacing stopped. MRI of the brain did not show RVP-related ischemia and the limited cTnI level increase normalized to preoperative values. Therefore, RVP during short periods of time seems to be a safe blood pressure-lowering technique for the brain and heart.

Effects of Stellate Ganglion Block on Analgesia Produced by Cervical Paravertebral Block as Established by Quantitative Sensory Testing: A Randomized Controlled Trial

Objective To use quantitative sensory testing (QST) to assess whether a stellate ganglion block (SGB) modulates the analgesia induced by cervical paravertebral block (CPVB). Design A prospective double-blind randomized controlled trial. Setting Department of Anesthesia, Antwerp University Hospital, October 2011 to December 2015. Subjects Twenty-eight adults scheduled for arthroscopy of a nonfractured shoulder were enrolled. Methods Participants were randomly assigned to receive either single CPVB (5 mL of levobupivacaine 0.5%) or combined CPVB + SGB (5 mL and 3 mL of levobubivacaine 0.5%, respectively). The detection thresholds for cold/warm sensations and cold/heat pain were established using thermal QST on the C4-C7 dermatomes before local anesthetic infiltration and at 0.5, 6, 10, and 24 hours thereafter. Our primary outcome was the time course of QST thresholds for the different neurosensitive/nociceptive modalities. As secondary and tertiary outcomes, we evaluated the degree of motor block and the time to first administration of rescue analgesics. Results We randomized 20 patients. There were no significant differences in the detection thresholds for the neurosensitive/nociceptive modalities, motor block, or timing for rescue analgesics between the groups (P = 0.15-0.94). All patients with CPVB + SGB exhibited Horners signs, whereas patients in the CPVB group did not exhibit these signs; however, this does not exclude sympathetic block. Conclusions We were unable to demonstrate any analgesic benefit of CPVB + SGB in arthroscopic shoulder surgery. It is therefore not unreasonable to suppose that pain from soft tissue injuries without bony lesions is transmitted mainly by somatic nerves with no or only minimal involvement of the sympathetic nervous system.

Imagem funcional da respiração após aceleração da recuperação do bloqueio neuromuscular com neostigmina ou sugamadex em ratos anestesiados: estudo piloto controlado e randomizado

OBJECTIVES Reductions in diaphragm activity are associated with the postoperative development of atelectasis. Neostigmine reversal is also associated with increased atelectasis. We assessed the effects of neostigmine, sugammadex, and spontaneous reversal on regional lung ventilation and airway flow. METHODS Six Sprague-Dawley rats were paralysed with rocuronium and mechanically ventilated until recovery of the train-of-four ratio to 0.5. We administered neostigmine (0.06mg.kg-1), sugammadex (15mg.kg-1), or saline (n=2 per group). Computed tomography scans were obtained during the breathing cycle. Three-dimensional models of lung lobes were generated using functional respiratory imaging technology, and lobar volumes were calculated during the breathing cycle. The diaphragmatic surface was segmented for the end-expiratory and end-inspiratory scans. The total change in volume was reported by the lung volume change from the end-expiratory scan to the end-inspiratory scan. Chest wall movement was defined as the lung volume change minus the volume change that resulted from diaphragm excursion. RESULTS The two rats that received neostigmine exhibited a smaller relative contribution of diaphragm movement to the total change in lung volume compared with the two rats that received sugammadex or saline (chest wall contribution (%): 26.69 and 25.55 for neostigmine; -2.77 and 15.98 for sugammadex; 18.82 and 10.30 for saline). CONCLUSION This pilot study in rats demonstrated an increased relative contribution of chest wall expansion after neostigmine compared with sugammadex or saline. This smaller relative contribution of diaphragm movement may be explained by a neostigmine-induced decrease in phrenic nerve activity or by remaining occupied acetylcholine receptors after neostigmine.