Ghislaine C. Echevarria

The effect of birthweight on childhood cognitive development in a middle-income country

BACKGROUND Intra-uterine growth is a powerful predictor of infant mortality and of health, developmental and socioeconomic outcomes in adulthood. The question about whether this relationship is causal rather than driven by unobserved characteristics of low-weight infants is, however, still open. We use twin models to examine the hypothesis that in utero growth has a detrimental impact on cognitive development in childhood. METHODS We merge birth registry information on birthweight with standardized Math and Spanish test scores for all fourth graders in Chile to create a prospective data set. Twin fixed-effects models are used to estimate the causal effect of intra-uterine growth on test scores. Fixed-effect estimates are compared with traditional regression results in a cross-section of births to gauge the omitted variable bias emerging from unobserved genetic, maternal and pregnancy-related factors in cross-sectional models. RESULTS Birthweight differences within twin pairs have a substantial effect on test scores. A 400-g increase in birthweight results in a 15% standard deviation increase in Math scores. The effect is larger among (estimated) monozygotic than dizygotic pairs, reaching >20% standard deviation. The effect varies across family socioeconomic status. It is strong among disadvantaged families but it nearly disappears among advantaged ones. CONCLUSION Scarcity of uterine resources resulting in intra-uterine growth restriction has a detrimental effect on cognitive development in childhood. This effect interacts with family socioeconomic status (SES), so that low-SES families reinforce the effect of low birthweight and high-SES families fully compensate for it. Findings are particularly relevant in the developing world, where intra-uterine growth restriction is the main determinant of low birthweight.

Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart

Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an α(2)-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30 min of regional ischemia followed by 120 min of reperfusion with dexmedetomidine before ischemia. The α(2)-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of α(2)-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and peri-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of α(2)-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine peri-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac α(2)-adrenergic receptor stimulation.

The relationship between neuraxial anesthesia and advanced ovarian cancer-related outcomes in the Chilean population.

BACKGROUND:Mixed evidence has been published relating the use of regional anesthesia during oncologic surgery to a decrease in time to cancer recurrence and improvement in overall survival. We investigated whether the use of epidural anesthesia, in addition to general analgesia during and/or after surgical removal of advanced ovarian cancer, has an impact on time to recurrence and overall survival. METHODS:Patients were identified from a prospective clinical registry. Eighty patients with advanced ovarian cancer (International Federation of Gynecologists and Obstetricians, stage IIIC and IV) undergoing surgery between January 2000 and March 2011 were studied. Propensity scoring (PS) methods (matching and inverse weighting) were used to compare the time to recurrence and overall survival of patients who did and did not receive epidural anesthesia and/or analgesia (EA), after controlling for selection bias. RESULTS:The median time to recurrence was 1.6 and 0.9 years for the EA and no EA groups, respectively (P = 0.02). After PS matching, the median time to recurrence was 1.6 and 1.4 years for the EA and no EA groups, respectively (P = 0.30). Similarly, PS weighting did not demonstrate an improvement in time to recurrence with the use of EA. Using a Cox proportional hazards model in the PS-matched sample, the estimated hazard ratio for EA exposure (0.72; 95% confidence interval [CI], 0.40–1.33) did not change substantially after adjusting for chemotherapy (0.73; 95% CI, 0.40–1.31). Similar results were obtained using PS weighting. The median survival time was 3.3 and 1.9 years for the EA and no EA groups, respectively (P = 0.01). After PS matching, the median survival time was 3.3 and 2.7 years for the EA and no EA groups, respectively (P = 0.37). Similarly, PS weighting did not demonstrate an improved survival with the use of EA. The estimated hazard ratio (0.74; 95% CI, 0.36–1.49) in the PS matched sample did not change substantially after adjusting for chemotherapy, with similar results when PS weighting was applied. CONCLUSIONS:After PS matching and weighting, we found no benefit in overall survival or time to recurrence in patients with advanced stages (International Federation of Gynecologists and Obstetricians IIIC and IV) of ovarian cancer after the use of EA during and after tumor debulking surgery.

Effect of intravenous fluid therapy on postoperative vomiting in children undergoing tonsillectomy

BACKGROUND Postoperative vomiting (POV) is one of the most frequent complications of tonsillectomy in children. The aim of this study was to evaluate the antiemetic effect of super-hydration with lactated Ringers solution in children undergoing elective otorhinolaryngological surgery. METHODS One hundred ASA I-II children, aged 1-12 yr, undergoing elective tonsillectomy, with or without adenoidectomy, under general anaesthesia were studied. Induction and maintenance of anaesthesia were standardized with fentanyl, mivacurium, and sevoflurane in N(2)O/O(2). Subjects were assigned to one of the two groups: 10 ml kg(-1) h(-1) lactated Ringers solution or 30 ml kg(-1) h(-1) lactated Ringers solution. A multivariable logistic regression was used for assessing the effects of super-hydration on POV (defined as the presence of retching, vomiting, or both). A value of P<0.05 was considered statistically significant. RESULTS During the first 24 h postoperative, the incidence of POV decreased from 82% to 62% (relative reduction of 24%, P=0.026). In the adjusted logistic regression model, subjects in the 10 ml kg(-1) h(-1) group had an odds ratio of POV that was 2.92 (95% confidence interval: 1.14, 7.51) for POV compared with subjects in the 30 ml kg(-1) h(-1) group. CONCLUSIONS Intraoperative administration of 30 ml kg(-1) h(-1) lactated Ringers solution significantly reduced the incidence of POV during the first 24 h postoperative. Our results support the use of super-hydration during tonsillectomy, as an alternative way to decrease the risk of POV in children.

Prospective evaluation of the time to peak effect of propofol to target the effect site in children.

Background: The plasma‐effect site equilibration rate constant (ke0) of propofol has been determined in children with the use of the time to maximum effect (tpeak), however, it has not been validated. The objective was to measure the tpeak; of propofol with two depths of anesthesia monitors in children and to evaluate these measurements with a target‐controlled infusion (TCI) system.

The Effective Effect-site Propofol Concentration for Induction and Intubation with Two Pharmacokinetic Models in Morbidly Obese Patients Using Total Body Weight

BACKGROUND:Most pharmacokinetic (PK) models used for propofol administration are based on studies in normal-weight patients. Extrapolation of these models for morbidly obese patients is controversial. Using 2 PK models and a target-controlled infusion system, we determined the predicted propofol effect-site concentration (Ce) needed for induction of anesthesia in morbidly obese subjects using total body weight. METHODS:Sixty-six morbidly obese subjects from 18 to 50 years of age were randomized to receive propofol to reach and maintain a predetermined propofol Ce, based on the PK models of either Marsh or Schnider. All patients were monitored with a Bispectral Index electroencephalographic monitor. Fentanyl 3 &mgr;g/kg total body weight was administered before starting the propofol infusion. After loss of consciousness, vecuronium was administered to facilitate endotracheal intubation. Groups of 6 patients each received propofol at a different, predetermined target propofol Ce. An “effective Ce” (ECe) was defined as the propofol Ce that provided adequate hypnosis (Bispectral Index <60) during the complete induction period (45 seconds after reaching the predetermined target Ce until 5 minutes after tracheal intubation). Heart rate and arterial blood pressure were measured every 1 minute throughout the study period. Probit regression analysis was performed to calculate the effective propofol Ce values to induce hypnosis in 50% (ECe50) and 95% (ECe95) of patients with 95% confidence intervals (CIs). RESULTS:Patient characteristics were similar between models and across the propofol target concentration groups. The ECe50 of propofol was 3.4 &mgr;g/mL (95% CI: 2.9, 3.7 &mgr;g/mL) with the Marsh model and 4.5 &mgr;g/mL (95% CI: 4.1, 4.8 &mgr;g/mL) with the Schnider model (P < 0.001). The ECe95 values were 4.2 &mgr;g/mL (95% CI: 3.8, 6.2 &mgr;g/mL) and 5.5 &mgr;g/mL (95% CI: 5.0, 7.2 &mgr;g/mL) with Marsh and Schnider models, respectively. At the ECe95, hemodynamic effects were similar with the 2 PK models. CONCLUSION:Different propofol target concentrations for each PK model must be used for induction when using total body weight in morbidly obese patients.

Early elevation of serum MMP-3 and MMP-12 predicts protection from World Trade Center-lung injury in New York City Firefighters: a nested case-control study.

Objective After 9/11/2001, some Fire Department of New York (FDNY) workers had excessive lung function decline. We hypothesized that early serum matrix metalloproteinases (MMP) expression predicts World Trade Center-Lung Injury (WTC-LI) years later. Methods This is a nested case-control analysis of never-smoking male firefighters with normal pre-exposure Forced Expiratory Volume in one second (FEV1) who had serum drawn up to 155 days post 9/11/2001. Serum MMP-1, 2,3,7,8, 9, 12 and 13 were measured. Cases of WTC-LI (N = 70) were defined as having an FEV1 one standard deviation below the mean (FEV1≤77%) at subspecialty pulmonary evaluation (SPE) which was performed 32 months (IQR 21–53) post-9/11. Controls (N = 123) were randomly selected. We modeled MMPs ability as a predictor of cases status with logistic regression adjusted for time to blood draw, exposure intensity, weight gain and pre-9/11 FEV1. Results Each log-increase in MMP-3 and MMP-12 showed reduced odds of developing WTC-LI by 73% and 54% respectively. MMP-3 and MMP-12 consistently clustered together in cases, controls, and the cohort. Increasing time to blood draw significantly and independently increased the risk of WTC-LI. Conclusions Elevated serum levels of MMP-3 and MMP-12 reduce the risk of developing WTC-LI. At any level of MMP-3 or 12, increased time to blood draw is associated with a diminished protective effect.

Dexametasona para profilaxis de náuseas y vómitos postoperatorios: efecto sobre la glicemia en pacientes con diabetes mellitus tipo 2 y en no diabéticos sometidos a cirugía laparoscópica

BACKGROUND Postoperative nausea and vomiting (PONV) prophylaxis with dexamethasone may produce significant hyperglycemia in the postoperative period. AIM To evaluate if this effect is of greater severity in type 2 diabetics compared with non-diabetic patients. MATERIAL AND METHODS Forty non-diabetic and thirty type 2 diabetic patients undergoing laparoscopic cholecystectomy were studied in a prospective and double-blind fashion manner. Patients were randomly distributed into 4 groups: Group I, non-diabetics control (n = 20), Group II, non-diabetics dexamethasone (n = 20), Group III, type 2 diabetics control (n = 15), and Group IV, type 2 diabetics dexamethasone (n = 15). Immediately after induction, patients in groups I and III received isotonic saline and patients in the dexamethasone groups received 8 mg i.v. of the steroid. Capillary blood glucose concentrations were measured at baseline and every 2 hours during the first 12 hours since the start of surgery. A linear mixed effect model, adjusted for baseline capillary glucose concentration, age and duration of surgery was used to analyze the data. RESULTS No effect of the presence of diabetes mellitus was observed in the evolution of glucose concentrations. There was a difference in capillary glucose concentrations between patients who received dexamethasone and placebo that started 2 hours post-intervention, reaching a mean maximum difference of 34 mg/dl (adjusted model, p < 0.001) at 10 hours post-intervention. CONCLUSIONS In this study, Type 2 diabetic patients did not show a higher susceptibility than non-diabetics to develop postoperative hyperglycemia after the use of prophylactic dexamethasone for PONV.

The Sensitivity of Motor Responses for Detecting Catheter-Nerve Contact During Ultrasound-Guided Femoral Nerve Blocks with Stimulating Catheters

BACKGROUND: We determined the sensitivity of motor responses evoked by stimulating catheters in determining catheter-nerve contact using ultrasonography as reference. METHODS: Femoral nerves were contacted using stimulating catheters under ultrasonography scanning in 25 patients. The output current was increased from its minimum until quadriceps muscle contraction occurred. The sensitivity of the motor response in determining catheter-nerve contact was calculated using 0.5 mA as current threshold. RESULTS: The current required for catheter stimulation to evoke a motor response ranged between 0.18 and 2.0 mA. Muscle contraction in response to 0.5 mA occurred in 16 of 25 subjects. The sensitivity of motor response for nerve stimulation was 64% (95% confidence interval: 0.43, 0.82). CONCLUSIONS: The absence of muscle responses at a stimulating current ⩽0.5 mA does not necessarily indicate the absence of catheter-nerve contact.

Obesity does not influence the onset and offset of sevoflurane effect as measured by the hysteresis between sevoflurane concentration and bispectral index.

BACKGROUND: The onset and offset of action of anesthetic gases might be delayed by respiratory changes and gas exchange alterations present in obese patients. In this study, we assessed the influence of obesity on the hysteresis between sevoflurane and its effect as measured by the bispectral index (BIS). Because the use of positive end-expiratory pressure (PEEP) in obese patients has improved gas exchange, we also assessed the influence of PEEP on hysteresis. METHODS: Fifteen obese and 15 normal-weight patients, ASA physical status I and II, 20 to 50 years old, scheduled to undergo general anesthesia for elective laparoscopic surgery, were prospectively studied. Anesthesia was induced with propofol and maintained with sevoflurane and fentanyl. At the end of surgery and after stable BIS values of 60 to 65, the inspired concentration of sevoflurane was increased to 5 vol% for 5 minutes or until BIS was <40 and then decreased. Sevoflurane transitions were performed once in normal-weight subjects (without PEEP) and twice in obese patients (one without PEEP and one with a PEEP of 8 cm H2O). The hysteresis between sevoflurane end-tidal concentrations and BIS during these transition periods was modeled with an inhibitory Emax model using a population pharmacokinetic/ pharmacodynamic (PK/PD) approach with NONMEM VI. A descriptive analysis of sevoflurane inspired and expired concentrations, BIS values, and time to reach different BIS end points was also used to compare the PK and PD characteristics. RESULTS: All patients completed the study. The data were adequately fit with the PK/PD model. The hysteresis expressed as the effect-site elimination rate constant was not influenced by body mass index or PEEP (P > 0.05). Neither obesity nor PEEP showed any influence on the PK/PD descriptors. CONCLUSIONS: Our results do not support the hypothesis that obesity prolongs induction or recovery times when sevoflurane, a poorly soluble anesthetic, is used to maintain anesthesia from 90 to 120 minutes.