H. Muñoz

Macrophage Inflammatory Protein‐1α in Term and Preterm Parturtition: Effect of Microbial Invasion of the Amniotic Cavity

PROBLEM: This study was conducted to determine whether: (1) gestational age, parturition, and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of immunoreactive macrophage inflammatory protein‐1α; (2) amniotic fluid concentrations of macrophage inflammatory protein‐1α are correlated with the white blood cell count and the concentrations of interleukin‐8 in amniotic fluid.

Renal function and cardiopulmonary bypass : effect of perfusion pressure

Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine less than 1.2 mg/dL, creatinine clearance greater than 70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary surgery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were measured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 +/- 36.7 in group 1 and 120.6 +/- 50.7 mL/min in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 +/- 39.7 mL/min, whereas in group 2 it increased to 157.6 +/- 79.5 mL/min; the difference between groups was significant. Early postoperatively, there was no difference: 136.2 +/- 86.6 mL/min in group 1 and 100 +/- 21.4 mL/min in group 2. One week postoperatively, values were 100.5 +/- 37.9 and 101.9 +/- 18.4, respectively. There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoperative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified.

Estimation of the plasma effect site equilibration rate constant (ke0) of propofol in children using the time to peak effect: comparison with adults.

Background:Targeting the effect site concentration may offer advantages over the traditional forms of administrating intravenous anesthetics. Because the lack of the plasma effect site equilibration rate constant (ke0) for propofol in children precludes the use of this technique in this population, the authors estimated the value of ke0 for propofol in children using the time to peak effect (tpeak) method and two pharmacokinetic models of propofol for children. Methods:The tpeak after a submaximal bolus dose of propofol was measured by means of the Alaris A-Line auditory evoked potential monitor (Danmeter A/S, Odense, Denmark) in 25 children (aged 3–11 yr) and 25 adults (aged 35–48 yr). Using tpeak and two previously validated sets of pharmacokinetic parameters for propofol in children, Kataria’s and that used in the Paedfusor (Graseby Medical Ltd., Hertfordshire, United Kingdom), the ke0 was estimated according to a method recently published. Results:The mean tpeak was 80 ± 20 s in adults and 132 ± 49 s in children (P < 0.001). The median ke0 in children was 0.41 min−1 with the model of Kataria and 0.91 min−1 with the Paedfusor model (P < 0.01). The corresponding t1/2 ke0 values, in minutes, were 1.7 and 0.8, respectively (P < 0.01). Conclusions:Children have a significantly longer tpeak of propofol than adults. The values of ke0 of propofol calculated for children depend on the pharmacokinetic model used and also can only be used with the appropriate set of pharmacokinetic parameters to target effect site in this population.

Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor

Lipid mediators play an important role in reproductive biology, especially, in parturition. Enhanced biosynthesis of eicosanoids, such as prostaglandin E2 (PGE2) and PGF2α, precedes the onset of labor as a result of increased expression of inducible cyclooxygenase 2 (COX‐2) in placental tissues. Metabolism of arachidonic acid results in bioactive lipid mediators beyond prostaglandins that could significantly influence myometrial activity. Therefore, an unbiased lipidomic approach was used to profile the arachidonic acid metabolome of amniotic fluid. In this study, liquid chromatography‐mass spectrometry was used for the first time to quantitate these metabolites in human amniotic fluid by comparing patients at midtrimester, at term but not in labor, and at term and in spontaneous labor. In addition to exposing novel aspects of COX pathway metabolism, this lipidomic study revealed a dramatic increase in epoxygenase‐ and lipoxygenasepathway‐derived lipid mediators in spontaneous labor with remarkable product selectivity. Despite their recognition as anti‐inflammatory lipid mediators and regulators of ion channels, little is known about the epoxygenase pathway in labor. Epoxygenase pathway metabolites are established regulators of vascular homeostasis in cardiovascular and renal physiology. Their presence as the dominant lipid mediators in spontaneous labor at term portends a yet undiscovered physiological function in parturition.—Maddipati, K. R., Romero, R., Chaiworapongsa, T., Zhou, S.‐L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Munoz, H., Honn, K. V., Eicosanomic profiling reveals dominance of the epoxygenase pathway in human amniotic fluid at term in spontaneous labor. FASEB J. 28, 4835–4846 (2014). www.fasebj.org

Performance of the cerebral state index during increasing levels of propofol anesthesia : A comparison with the bispectral index

BACKGROUND:The cerebral state monitor is a new device to measure depth of anesthesia. In this study we compared the cerebral state monitor with the bispectral index (BIS) monitor during propofol anesthesia. METHODS:Fifteen healthy patients received a continuous infusion of propofol (300 mL/h). The cerebral state index (CSI) and the BIS values were recorded until burst suppression ratio ≥60%. Baseline variability, prediction probability, and agreement analysis between indices were evaluated. Clinical markers of loss of consciousness were also assessed. RESULTS:Mean awake BIS and CSI values were 95.6 and 91.6, respectively (P = 0.01). BIS and CSI prediction probability values (mean ± sd) were estimated to be 0.87 ± 0.08 and 0.86 ± 0.08, respectively (NS). The CSI tended to stabilize at values of 60–40 when estimated propofol concentrations at the effect site increased from 5 to 8 &mgr;g/mL. The BIS stabilized at values of 40–20 when the propofol concentrations at the effect site increased from 7 to 10 &mgr;g/mL. The mean BIS-CSI difference was −7.4 with 95% limits of agreement of 22.2 and −36.9. The BIS and CSI correlation with the burst suppression ratio was −0.60 and −0.97, respectively (P < 0.01). Predicted BIS and CSI values for loss of eyelash reflex in 50% and 95% of the patients were different (P < 0.05). CONCLUSION:The overall performance of both monitors during propofol induction was similar. However, the different dynamic profiles of these monitors indicate that BIS may be a more useful index for evaluating intermediate anesthetic levels, whereas CSI may be better for evaluating deeper anesthetic levels.

Remifentanil Requirements during Sevoflurane Administration to Block Somatic and Cardiovascular Responses to Skin Incision in Children and Adults

Background The authors found no studies comparing intraoperative requirements of opioids between children and adults, so they determined the infusion rate of remifentanil to block somatic (IR50) and autonomic response (IRBAR50) to skin incision in children and adults. Methods Forty-one adults (aged 20–60 yr) and 24 children (aged 2–10 yr) undergoing lower abdominal surgery were studied. In adults, anesthesia induction was with sevoflurane during remifentanil infusion, whereas in children remifentanil administration was started after induction with sevoflurane. After intubation, sevoflurane was administered in 100% O2 and was adjusted to an ET% of 1 MAC-awake corrected for age at least 15 min before surgery. Patients were randomized to receive remifentanil at a rate ranging from 0.05 to 0.35 &mgr;g · kg−1 · min−1 for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic and autonomic responses were observed. The somatic response was defined as positive with any gross movement of extremity, and the autonomic response was deemed positive with any increase in heart rate or mean arterial pressure equal to or more than 10% of preincision values. Using logistic regression, the IR50 and IRBAR50 were determined in both groups of patients and compared with unpaired Student t test. A P value less than 0.05 was considered significant. Results The IR50 ± SD was 0.10 ± 0.02 &mgr;g · kg−1 · min−1 in adults and 0.22 ± 0.03 &mgr;g · kg−1 · min−1 in children (P < 0.001). The IRBAR50 ± SD was 0.11 ± 0.02 &mgr;g · kg−1 · min−1 in adults and 0.27 ± 0.06 &mgr;g · kg−1 · min−1 in children (P < 0.001). Conclusions To block somatic and autonomic responses to surgery, children require a remifentanil infusion rate at least twofold higher than adults.

Remifentanil requirements during propofol administration to block the somatic response to skin incision in children and adults.

BACKGROUND:During sevoflurane administration, children require a remifentanil infusion rate twofold higher than adults to block responses to skin incision. Similar data concerning remifentanil requirements are unavailable during total IV anesthesia. METHODS:We prospectively determined the infusion rate (IR) of remifentanil necessary to block the somatic response to skin incision in 50% (IR50) of adults (n = 20, aged 20–60 yr) and children (n = 20, aged 3–11 yr) during propofol anesthesia. In each patient undergoing lower abdominal surgery, a remifentanil infusion was initiated, followed by target-controlled infusion of propofol set at a plasma concentration of 6 &mgr;g/mL. After tracheal intubation, propofol was reduced to 3 &mgr;g/mL until the end of the study. Remifentanil IR was determined according to Dixons up-and-down method, with the first patient in each group receiving 0.2 &mgr;g · kg−1 · min−1 followed by the consecutive patient receiving 0.02 &mgr;g · kg−1 · min−1 modifications according to the response of the previous patient. The remifentanil IR was kept unchanged for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic response was observed. If there was any gross movement of extremity the response was considered positive. RESULTS:The IR50 (CI95%) was 0.08 (0.06–0.12) &mgr;g · kg−1 · min−1 in adults and 0.15 (0.13–0.17) &mgr;g · kg−1 · min−1 in children (P < 0.001). CONCLUSION:These results demonstrate that, similar to sevoflurane anesthesia, during total IV anesthesia with propofol, children require a remifentanil IR almost twofold higher than adults to block the somatic response to skin incision.

Beare-Stevenson syndrome: Two south american patients with FGFR2 analysis

We report two patients with Beare‐Stevenson syndrome. This syndrome presents craniosynostosis with or without clover‐leaf skull, craniofacial anomalies, cutis gyrata, acanthosis nigricans, prominent umbilical stump, furrowed palms and soles, genital and anal anomalies. Both female newborn patients presented at birth with craniofacial anomalies, variable cutis gyrata in forehead and preauricular regions, prominent umbilical stump and anogenital anomalies. Furrowed palms and soles were also observed. The radiologic examination showed a cloverleaf‐form craniosynostosis. Chromosomes were normal. They were born with respiratory distress and were connected to mechanical ventilation for ventilatory support. Both of them died in 50 days after birth due to secondary complications. The molecular analysis of these patients identified the mutation Tyr375Cys in the FGFR2 gene.

5-Hydroxyeicosatetraenoic acid and human parturition

5-Hydroxyeicosatetraenoic acid (5-HETE) is an arachidonic acid (AA) metabolite derived from the lipoxygenase pathway which is capable of inducing uterine contractions. The purpose of this study was to determine a). whether 5-HETE concentrations in amniotic fluid increase before or after the onset of labor and b). whether acetylsalicylic acid (ASA) could modulate the production of 5-HETE by human amnion cells. 5-HETE concentrations are increased in amniotic fluid before the onset of labor. Furthermore, ASA treatment as expected inhibited PGE2, but also significantly increased 5-HETE production by amnion cells. 5-HETE concentrations on average increased by greater than 2.5 fold (p < 0.001) in amniotic fluid prior to spontaneous labor when compared with samples obtained from the same patients earlier in gestation and therefore may be important in mechanisms regulating the onset of labor. ASA provokes an increase in 5-HETE biosynthesis by amnion cells: control media 2.60 +/- 1.5, ASA treatment alone 5.17 +/- 0.20, IL-1 beta alone 6.39 +/- 2.1, and ASA + IL-1 beta 8.95 +/- 1.2 (mean +/- SEM) picograms per microgram protein per 16 hours. These findings may explain in part why cyclooxygenase inhibitors are not always successful in treating women with preterm labor.

Screening for trisomy 21 during the routine second-trimester ultrasound examination in an unselected Chilean population

To evaluate the performance of a detailed ultrasound examination during the second trimester as a screening test for Down syndrome in an unselected Chilean population.