Characterization of infant spinal anesthesia using surface electromyography: An observational study.

BACKGROUND: As the risks of general anesthesia in infants become clearer, pediatric anesthesiologists are seeking alternatives. Though infant spinal anesthesia is one such alternative, its use is limited by its perceived short duration. Prior studies investigating infant spinal anesthesia are open to interpretation and may not have accurately characterized block onset or density. Surface electromyography is a passive, noninvasive modality that can measure the effects of neural blockade. AIMS: To quantitatively describe the onset, density, and duration of infant spinal anesthesia using surface electromyography. METHODS: In this observational study, 13 infants undergoing lower abdominal surgery received spinal anesthesia (0.5% bupivacaine with clonidine). Surface electromyography collected continuous data at T2, right T8, left T8, and L2. Data were processed in MATLAB. Onset, density, and duration were defined as the mean derivative within the first 30 s after block administration, the maximum difference in signal compared with preblock baseline, and the time elapsed between block administration and the return of a persistent signal to 50% above the maximum difference, respectively. RESULTS: Mean patient age and weight were 7.5 ± 2.6 months and 8.0 ± 2.2 kg, respectively. All patients were male. There was a statistically significant difference in the average rate of spinal anesthesia onset (mean percent decrease per second [95% confidence interval]) between myotomes (F (3, 35) = 7.42, p < .001): T2 = 15.93 (9.23, 22.62), right T8 = 20.98 (14.52, 27.44), left T8 = 17.92 (11.46, 24.38), L2 = 32.92 (26.46, 39.38). There was a statistically significant difference in mean surface electromyography signal (mean decibels, 95% confidence interval) across both pre- and postspinal anesthesia Timepoints between myotomes (F (3, 36) = 32.63, p < .0001): T2 = 45.05 (38.92, 51.18), Right T8 = 41.26 (35.12, 47.39), Left T8 = 43.07 (36.93, 49.20), L2 = 22.79 (16.65, 28.92). Within each myotome, there was statistically significant, near complete attenuation of sEMG signal due to spinal anesthesia: T2 mean (pre-post) difference: mean decibels (95% confidence interval) = 39.53 (28.87, 50.20), p < .0001, right T8 = 51.97 (41.30, 62.64), p < .0001, left T8 = 46.09 (35.42, 56.76), p < .0001, L2 = 44.75 (34.08, 55.42), p < .0001. There was no statistically significant difference in mean (pre-post) differences between myotomes. The mean duration of spinal anesthesia lasted greater than 90 min and there was no statistical difference between myotomes. There were also no statistically significant associations between age and weight and onset or duration. CONCLUSIONS: Surface electromyography can be used to characterize neural blockade in children. Importantly, these results suggest that awake infant spinal anesthesia motor block lasts, conservatively, 90 min. This exploratory study has highlighted the potential for expanding awake infant spinal anesthesia to a broader range of procedures and the utility of surface electromyography in studying regional anesthesia techniques.

Electroencephalographic assessment of infant spinal anesthesia: A pilot prospective observational study.

INTRODUCTION: Spinal anesthesia is utilized as an alternative to general anesthesia in infants for some surgeries. After spinal anesthesia, infants often become less conscious without administration of sedative medications. The aim of this study was to assess electroencephalographic (EEG) correlates after spinal anesthesia in a cohort of infants. PATIENTS AND METHODS: This pilot study included 12 infants who underwent spinal anesthesia. Unprocessed electroencephalography was recorded. The electroencephalogram was interpreted by four neurologists. Processed analyses compared electroencephalogram changes 30 min after spinal anesthesia to baseline. RESULTS: Following spinal anesthesia, all 12 infants became sedated. Electroencephalography in all 12 demonstrated Stage 2 sleep with the appearance of sleep spindles (12-14 Hz) in the frontal and central leads in 8/12 (67%) of subjects. The median time to onset of sleep spindles was 24.7 interquartile range (21.2, 29.9) min. The duration of sleep spindles was 25.1 interquartile range (5.8, 99.8) min. Voltage attenuation and background slowing were the most common initial changes. Compared to baseline, the electroencephalogram 30 min after spinal anesthesia showed significantly increased absolute delta power (p = 0.02) and gamma power (p < 0.0001); decreases in beta (p = 0.0006) and higher beta (p < 0.0001) were also observed. The Fast Fourier Transform power ratio difference for delta/beta was increased (p = 0.03). Increased coherence was noted in the delta (p = 0.02) and theta (p = 0.04) bandwidths. DISCUSSION: Spinal anesthesia in infants is associated with increased electroencephalographic slow wave activity and decreased beta activity compared to the awake state, with appearance of sleep spindles suggestive of normal sleep. The etiology and significance of the observed voltage attenuation and background slowing remains unclear. CONCLUSIONS: The EEG signature of infant spinal anesthesia is distinct from that seen with general anesthesia and is consistent with normal sleep. Further investigation is required to better understand the etiology of these findings. Our preliminary findings contribute to the understanding of the brain effects of spinal anesthesia in early development.

Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study.

PURPOSE: To evaluate the effects of sex on miRNA expression in the hippocampus after isoflurane anesthesia in a neonatal piglet model. METHODS: Six male and 6 female piglets, aged 3-5 days, were anesthetized with 2% isoflurane in room air for 3 h. Full physiologic monitoring was observed. Untreated animals (6 male, 6 female) served as controls. Expression of miRNAs in hippocampus was assessed. RESULTS: In controls, miRNA expression in the hippocampus was highly conserved between males and females. However, 17/326 displayed sex-dependent differences: 10 miRNAs were more highly expressed in males; 7 showed lower expression in males than females. Isoflurane was associated with changes in the expression of distinct subsets of miRNAs in both males and females. In females, 14/326 miRNAs were significantly changed (3 downregulated; 11 upregulated); in males, 17/326 miRNAs were changed (7 downregulated; 10 upregulated). There was no overlap in significantly changed miRNAs between isoflurane-exposed males and females. CONCLUSIONS: In the neonatal piglet hippocampus, miRNA expression was highly conserved. There was no overlap in miRNA expression between isoflurane-exposed males and females, suggesting sex differences in isoflurane-induced miRNA expression. These results support the hypothesis that a clinically relevant exposure to isoflurane induces distinct miRNA signatures in the hippocampus of neonatal male and female piglets. Their functional relevance in anesthesia-induced neurotoxicity remains unknown, although changes in specific miRNAs may either contribute to or protect against anesthesia-induced neurotoxicity.

Spinal anesthesia for surgery longer than 60 min in infants: experience from the first 2 years of a spinal anesthesia program.

PURPOSE: Spinal anesthesia (SA) is being increasingly used in infants to avoid the potential negative neurocognitive effects of general anesthesia (GA). However, SA has been reported to provide a relatively short duration of surgical anesthesia. METHODS: We retrospectively reviewed SA cases for surgical procedures lasting more than 60 min in children up to 3 years old. All patients received bupivacaine 0.5% (1 mg/kg up to 7 mg) with clonidine 1 µg/kg ± epinephrine. The primary outcome was success of SA without subsequent conversion to GA. RESULTS: Thirty-five patients met inclusion criteria (all males, age 7 ± 5 months, weight 8 ± 2 kg). Procedures included male genital, groin and multiple site surgeries. Average surgical duration was 71 ± 12 min (range 60-111 min). SA was successful in 31 of 35 patients (89%; 95% confidence interval 78, 99%). The cause of failure was rarely due to the duration of surgery (1 of 4 patients). Six patients with successful SA required sedation with dexmedetomidine ± fentanyl. Differences in procedure duration and patient characteristics were not statistically significant between successful and failed SA. CONCLUSIONS: SA is a highly successful technique and may offer an alternative to GA in children undergoing appropriate surgery expected to last as long as 60-100 min.

Changes in tissue and cerebral oxygenation following spinal anesthesia in infants: a prospective study.

Use of spinal anesthesia (SA) in children may address concerns about potential neurocognitive effects of general anesthesia. We used near-infrared spectroscopy (NIRS) to assess the effects of SA on cerebral and tissue oxygenation in 19 patients aged 7 ± 3 months. Prior to SA placement, NIRS monitors were placed on the forehead (cerebral) and the thigh (tissue). Intraoperative cerebral and tissue saturation were 73 ± 7 and 80 ± 11%, respectively, before SA placement. NIRS measurements were monitored every minute for 30 min after SA placement and modeled using mixed-effects linear regression. Regression estimates showed that cerebral saturation remained stable from 67% [95% confidence interval (CI) 63, 71%] after SA placement to 68% (95% CI 65, 72%) at the conclusion of monitoring. After SA placement, tissue saturation was elevated compared to baseline values; but further change [from 91% (95% CI 89, 93%) to 93% (95% CI 91, 95%) at the end of monitoring] was clinically non-significant. All patients breathed spontaneously on room air without changes in oxygen saturation. Blood pressure and heart rate decreased after SA placement, but no changes in hemodynamic parameters required treatment. These data provide further evidence of the neutral effect of SA on cerebral oxygenation 30 min after block placement.

Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender.

BACKGROUND: Clopidogrel is an irreversible antagonist of P2Y12 receptors (P2Y12Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y12Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function. AIM: To evaluate if blockade of P2Y12Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS). METHODS: A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y12R distribution in human gut. RESULTS: The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis (p ≤ 0.0001) and psychogenic pain (p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/p = 0.008; diarrhea, flatulence, p = 0.01). P2Y12R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y12Rs expressed in Females â‰« Males. CONCLUSIONS: Irreversible blockade of P2Y12R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y12Rs in IBS.

Selective induction of IL-1ß after a brief isoflurane anesthetic in children undergoing MRI examination.

PURPOSE: To determine if isoflurane anesthesia without surgery causes systemic inflammation in children. Inflammation is targeted as responsible for the development of many neurologic pathologies. The effect will be evaluated by measuring serum cytokine levels before and after isoflurane anesthesia. The possible neurotoxic effect of anesthetic agents is a concern in pediatric anesthesia. Questions remain as to the true effects of anesthesia alone on systemic inflammation. The current study assesses systemic inflammatory response to general anesthesia in children not exposed to surgical stress. METHODS: Twenty-five patients, aged 6 months to 11 years undergoing MRI scanning were recruited. Patients with ASA Physical Status Classification >II, known neurologic disease, prematurity, recent infection, or current treatment with anti-inflammatory medications were excluded. Each patient received a sevoflurane induction, peripheral intravenous catheterization, and laryngeal mask airway placement. Isoflurane was titrated to ensure adequate depth of anesthesia. Two peripheral blood samples were obtained: one immediately after placement of the PIV and one upon arrival to the post-anesthesia care unit. Serum cytokine levels were compared between pre- and post-isoflurane time points using paired t tests. RESULTS: For all patients, interleukin-1ß increased after isoflurane when compared to pre-isoflurane samples (pre = 25.97 ± 9.01, post = 38.53 ± 16.56, p = 0.0002). Serum levels of IL-6 (pre = 2.28 ± 2.27, post = 2.04 ± 2.15, p = 0.146) and tumor necrosis factor-α (pre = 94.26 ± 18.07, post = 85.84 ± 12.12, p = 0.057) were not significantly changed. Interleukin-10 and vascular endothelial growth factor were undetectable in pre- and post-isoflurane samples at a minimum detection threshold of 6.6 and 10 pg/ml, respectively. CONCLUSIONS: A brief (approximately 60 min) exposure to isoflurane general anesthesia, without induced surgical stress, significantly increased serum IL-1ß, a selective activation marker of systemic inflammation (IL-1ß pathway).

A Single Center's Experience With Spinal Anesthesia for Pediatric Patients Undergoing Surgical Procedures.

PURPOSE: To perform a single institution review of spinal instead of general anesthesia for pediatric patients undergoing surgical procedures. Spinal success rate, intraoperative complications, and postoperative outcomes including unplanned hospital admission and emergency department visits within seven days are reported. METHODS: Retrospective chart review of pediatric patients who underwent spinal anesthesia for surgical procedures from 2016 until 2022. Data collected included patient demographics, procedure and anesthetic characteristics, intraoperative complications, unplanned admissions, and emergency department returns. RESULTS: The study cohort included 1221 patients. Ninety-two percent of the patients tolerated their surgical procedure without requiring conversion to general anesthesia, and 78% of patients that had spinals placed successfully did not receive any sedation following lumbar puncture. The most common intraoperative event was systolic blood pressure below 60 mm Hg (14%), but no cases required administration of vasoactive agents, and no serious intraoperative adverse events were observed. Post-Anesthesia Care Unit Phase I was bypassed in 72% of cases with a median postoperative length of stay of 84 min. Forty-six patients returned to the emergency department following hospital discharge, but no returns were due to anesthetic concerns. CONCLUSIONS: Spinal anesthesia is a viable and versatile option for a diversity of pediatric surgical procedures. We noted a low incidence of intraoperative and postoperative complications. There remain numerous potential advantages of spinal anesthesia over general anesthesia in young pediatric patients particularly in the ambulatory setting. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective cohort treatment study.

Cerebral Blood Flow Autoregulation in Offspring From Experimentally Preeclamptic Rats and the Effect of Age.

Preeclampsia is a hypertensive disorder of pregnancy that causes significant, long term cardiovascular effects for both the mother and offspring. A previous study demonstrated that middle cerebral arteries in offspring from an experimental rat model of preeclampsia were smaller, stiffer, and did not enlarge over the course of maturation, suggesting potential hemodynamic alterations in these offspring. Here we investigated the effect of experimental preeclampsia on cerebral blood flow autoregulation in juvenile and adult offspring that were born from normal pregnant or experimentally preeclamptic rats. Relative cerebral blood flow was measured using laser Doppler flowmetry, and cerebral blood flow autoregulation curves were constructed by raising blood pressure and controlled hemorrhage to lower blood pressure. Immunohistochemistry was used to assess middle cerebral artery size. Heart rate and blood pressure were measured in awake adult offspring using implanted radiotelemetry. Serum epinephrine was measured using enzyme-linked immunosorbent assay. Offspring from both groups showed maturation of cerebral blood flow autoregulation as offspring aged from juvenile to adulthood as demonstrated by the wider autoregulatory plateau. Experimental preeclampsia did not affect cerebral blood flow autoregulation in juvenile offspring, and it had no effect on cerebral blood flow autoregulation in adult offspring over the lower range of blood pressures. However, experimental preeclampsia caused a right shift in the upper range of blood pressures in adult offspring (compared to normal pregnant). Structurally, middle cerebral arteries from normal pregnant offspring demonstrated growth with aging, while middle cerebral arteries from experimentally preeclamptic offspring did not, and by adulthood normal pregnant offspring had significantly larger middle cerebral arteries. Middle cerebral artery lumen diameters did not significantly change as offspring aged. Serum epinephrine was elevated in juvenile experimentally preeclamptic offspring, and a greater degree of hemorrhage was required to induce hypotension, suggesting increased sympathetic activity. Finally, despite no evidence of increased sympathetic activity, adult experimentally preeclamptic offspring were found to have persistently higher heart rate. These results demonstrate a significant effect of experimental preeclampsia on the upper range of autoregulation and cerebrovascular structure in juvenile and adult offspring that could have an important influence on brain perfusion under conditions of hypo and/or hypertension.

Abnormal development of cerebral arteries and veins in offspring of experimentally preeclamptic rats: Potential role in perinatal stroke.

Preeclampsia, a hypertensive disorder of pregnancy, complicates up to 10 % of all pregnancies and increases the risk for perinatal stroke in offspring. The mechanism of this increase is unknown, but may involve vascular dysfunction. The goal of this study was to evaluate the effect of experimental preeclampsia (ePE) on cerebrovascular function in offspring to eludciate a possible mechanism for this association. Dams were fed a high cholesterol diet beginning on day 7 of gestation to induce experimental preeclampsia. Middle cerebral arteries (MCA) and the Vein of Galen (VoG) were isolated from pups from ePE dams and compared to pups from normal pregnant (NP) dams at postnatal days 16, 23, and 30 and studied pressurized in an arteriograph chamber. Markers of inflammation and oxidative stress were measured in serum. Our results suggest altered structure and function in both MCA and VoG of ePE pups. We also found evidence of systemic inflammation and oxidative stress in ePE pups. These findings provide a potential link between preeclampsia and the occurrence or severity of perinatal stroke.

Perinatal stroke.

Perinatal stroke is a heterogeneous syndrome resulting from brain injury of vascular origin that occurs between 20 weeks of gestation and 28 days of postnatal life. The incidence of perinatal stroke is estimated to be between 1:1600 and 1:3000 live births (approximately 2500 children per year in the United States), though its actual incidence is difficult to estimate because it is likely underdiagnosed. Perinatal arterial ischemic stroke (PAIS) accounts for approximately 70% of cases of perinatal stroke. Cerebral sinovenous thrombosis, while less common, also accounts for a large proportion of the morbidity and mortality seen with perinatal stroke. Hemorrhagic stroke leads to disruption of neurologic function due to intracerebral hemorrhage that is nontraumatic in origin. While most cases of PAIS fall into one of these three categories, other patterns of injury should also be considered perinatal stroke. In some cases, the etiology of PAIS is not known but is idiopathic. This chapter will review the classification, risk factors, pathogenesis, clinical presentation, management, and long-term sequelae of perinatal stroke.

Single-Shot Spinal Anesthesia in an Infant Requiring Magnetic Resonance Imaging and Open Lower-Extremity Surgery: A Case Report.

Spinal anesthesia (SA) is a safe and effective anesthetic technique for lower abdominal and lower extremity surgery in neonates and infants and is associated with an apparent state of sedation. We report the use of single-shot SA in a 6-week-old infant for a combined magnetic resonance imaging and open surgical biopsy of a deep soft tissue lower extremity mass. By leveraging the unique qualities of SA (sedation and surgical blockade), we avoided the need for general anesthesia. To our knowledge, this is the first reported use of single-shot SA for an infant undergoing two procedures in the same day.

Epidural and Spinal Anesthesia for Newborn Surgery.

Neuraxial (spinal and epidural) anesthesia has become commonplace in the care of neonates undergoing surgical procedures. These techniques afford many benefits, and, when properly performed, are extremely safe. This article reviews the benefits, risks, and applications of neuraxial anesthesia in neonates.

Adaptation of Microelectrode Array Technology for the Study of Anesthesia-induced Neurotoxicity in the Intact Piglet Brain.

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain. This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the mechanism(s) of anesthesia-induced neurotoxicity (AIN). MEAs enable real-time monitoring of in vivo neurotransmitter activity and offer exceptional temporal and spatial resolution. It is hypothesized that anesthetic neurotoxicity is caused in part by glutamate dysregulation and MEAs offer a method to measure glutamate. The novel implementation of MEA technology in a piglet model presents a unique opportunity for the study of AIN.

Spinal anesthesia after intraoperative cardiac arrest during general anesthesia in an infant.

Although generally safe and effective, severe perioperative complications, including cardiac arrest, may occur during general anesthesia in infants. With the emergence of evidence that specific anesthetic agents may affect future neurocognitive outcomes, there has been an increased focus on alternatives to general anesthesia, including spinal anesthesia. We present a case of cardiac arrest during general anesthesia in an infant who required urologic surgery. During the subsequent anesthetic care, spinal anesthesia was offered as an alternative to general anesthesia. The risks of severe perioperative complications during general anesthesia are reviewed, etiologic factors for such events are presented, and the use of spinal anesthesia as an alternative to general anesthesia is discussed.

Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach.

Anesthesia cannot be avoided in many cases when surgery is required, particularly in children. Recent investigations in animals have raised concerns that anesthesia exposure may lead to neuronal apoptosis, known as anesthesia-induced developmental neurotoxicity (AIDN). Furthermore, some clinical studies in children have suggested that anesthesia exposure may lead to neurodevelopmental deficits later in life. Nonetheless, an ideal animal model for preclinical study has yet to be developed. The neonatal piglet represents a valuable model for preclinical study, as they share a striking number of developmental similarities with humans. The anatomy and physiology of piglets allow for implementation of rigorous human perioperative conditions in both survival and non-survival procedures. Femoral artery catheterization allows for close monitoring, thus enabling prompt correction of any deviation of the piglet's vital signs and chemistries. In addition, there are multiple developmental similarities between piglets and human neonates. The techniques required to use piglets for experimentation will require experience to master. A pediatric anesthesiologist is a critical member of the investigative team. We describe, in a general sense, the appropriate use of a piglet model for neurodevelopmental study.

Spinal anesthesia for pediatric urological surgery: Reducing the theoretic neurotoxic effects of general anesthesia.

BACKGROUND: Spinal anesthesia (SA) is an effective technique that has been used in children for years. With growing concern with regard to the risks of general anesthesia (GA), we developed a SA program to provide an alternative option. We present our initial experience with this program. OBJECTIVE: To implement a SA program at a large tertiary care pediatric center and assess the safety and efficacy of the technique as an alternative to GA for urologic surgery. STUDY DESIGN/METHODS: We prospectively collected data on all children undergoing SA at our institution. We recorded demographics, procedure, time required for placement of the SA, length of surgery, success of lumbar puncture, success of attaining adequate surgical anesthesia, need for supplemental systemic sedation, conversion to GA, and perioperative complications. RESULTS: SA was attempted in 105 consecutive children (104 boys, 1 girl) with a mean age of 7.4 ± 4.3 months (range 19 days-24 months) and mean weight of 8.3 ± 1.7 kg (range 3.5-13.7). Placement of the SA was successful in 93/105 children (89%). Inability to achieve lumbar puncture (cerebrospinal fluid was not obtained) meant that SA was abandoned in seven (7%) patients and GA was administered. In five patients in whom SA was successful and surgery was begun, 5/93 (5%) required conversion to GA: two because of evisceration of intestine through large hernia defects related to coughing and abdominal irritation, two because of lack of motor blockade despite an adequate sensory block, and one because of an inability to place an intravenous catheter in the lower extremities (required per SA protocol). If necessary, an intravenous catheter can be placed in the upper extremity, but this must be weighed against the fact that the block has already been placed and is of limited duration. Overall, SA was successful (SA was placed and surgery was completed without conversion to GA) in 88/105 children (84%). No additional sedation and no systemic anesthetic agents were required in 75/88 children (85%). The average time required to place the SA was 3.8 ± 2.7 min (range 1-12). The average time for the surgical procedure was 38.3 ± 23.1 min (range 10-122). No patient required conversion to GA because of recession of block. There were no surgical complications. DISCUSSION/CONCLUSIONS: SA is a safe and efficacious technique for routine pediatric urological procedures. SA should be considered for cases such as neonatal torsion or patients with significant cardiac or pulmonary comorbidities when the risks of GA are often weighed against the risks of non-intervention.

The accuracy of the central landmark used for central venous catheterization of the internal jugular vein.

We simulated needle paths based on the central landmark used for central venous catheterization of the internal jugular vein. We obtained ultrasound images to quantify the landmark's accuracy (precision and bias) in 107 subjects placed in Trendelenburg position with their heads turned 30-35 degrees. We also determined the frequency of simulated carotid artery puncture. The simulated needle path missed the middle 80% of the lumen of the internal jugular vein in 34% of subjects (95% confidence interval [CI], 25% to 44%) and traversed the carotid artery in 26% of subjects (95% CI, 18% to 35%). Both events occurred in 20% of subjects (95% CI, 13%-29%). The landmark had a medial bias of 3.7 mm (95% CI, 2.7 to 4.8); it was more often (77 of 104 subjects) medial to the center of the right internal jugular vein (P < 0.001). The landmark was more likely to miss the internal jugular vein (odds ratio, 3.11; P < 0.016) and intersect the carotid (odds ratio, 3.03; P < 0.024) in obese patients. The central landmark should not be expected to yield frequent success on first needle pass without risk of carotid puncture because of its imprecision and bias. The measured bias should be considered when the central landmark is used for central venous catheterization.

A novel, clinically relevant use of a piglet model to study the effects of anesthetics on the developing brain.

BACKGROUND: Anesthesia-induced neurotoxicity research in the developing brain must rely upon an unimpeachable animal model and a standardized treatment approach. In this manner, identification of mechanisms of action may be undertaken. The goal of this study was to develop a novel, clinically relevant, translational way to use a piglet model to investigate anesthesia effects on the developing brain. METHODS: 29 newborn piglets were assigned to either: (1) control (no intervention, n = 10); (2) lipopolysaccharide (LPS; positive inflammatory control, n = 9); or (3) isoflurane anesthesia (n = 10). Positive inflammatory control animals were given 100 mcg/kg LPS from Escherichia coli intraperitoneally (IP) on the same day as those receiving isoflurane. Isoflurane was administered for 3 h while care was taken to ensure human perioperative conditions. To establish a clinical scenario, each animal was intubated and monitored with pulse oximetry, invasive and non-invasive blood pressure, electrocardiogram, temperature, end-tidal CO2, anesthetic concentration, and iSTAT blood analysis. All animals were sacrificed after 48 h using transcardiac perfusion of ice-cold, heparinized phosphate buffered saline (PBS) followed by 4 % paraformaldehyde (PFA). Brains were collected and histopathological analysis focused on the entorhinal cortex looking for degenerative changes due to its critical role in learning and memory. Reliable identification of entorhinal cortex was achieved by using colored ink on the surface of the brains, which was then cross-referenced with microscopic anatomy. Hematoxylin & eosin-stained high-power fields was used to quantify cells. ImageJ™ (National Institutes of Health, Bethesda, MD, USA) was used to count absolute number of progenitor glial cells (PGC) and number of PGCs per cluster. Immunohistochemistry was also utilized to ensure positive identification of cellular structures. RESULTS: Histopathological sections of 28 brains were analyzed. One animal in the LPS group died shortly after administration, presumably from inadvertent intravascular injection. There was an acute basal ganglia ischemic infarct in one isoflurane-treated animal. A large number of small, round nucleated cells were seen throughout layer II of the entorhinal cortex in all animals. These cells were identified as PGCs using immunohistochemistry and light microscopy. Although there was no difference in the absolute number of PGCs between the groups, animals given isoflurane or LPS demonstrated a significant increase in cells forming 'clusters' in the entorhinal cortex. An apparent change in the pattern of doublecortin labeling also suggests changes in neuronal precursors and undifferentiated neurons. CONCLUSIONS: This study represents the first novel use of a clinically relevant neonatal piglet model to study anesthesia effects on the developing brain. LPS induces neuroinflammation, and this is a potential mechanism for LPS and perhaps isoflurane in causing a change in progenitor cell distribution. We postulate that the isoflurane-induced change in glial progenitor cell distribution could have important implications for cell differentiation, maturation and neural circuit behavior in the rapidly developing brain.

Devazepide fails to reverse the inhibitory effect of interleukin-1beta on food intake in female rats.

Proinflammatory cytokines released during the course of infection elicit numerous behavioral and metabolic changes. The decrease in food intake that accompanies infection is mediated in part by interleukin-1 (IL-1). Cholecystokinin (CCK) is a neuropeptide released during a meal, decreases food intake, and previous research suggests that CCK mediates the anorectic action of IL-1. The effects of estrogen on food intake are also thought to involve CCK, as the satiety action of CCK is increased by estradiol in both intact and ovariectomized rats. Estradiol also modulates many of the behavioral and physiological effects of IL-1. The present experiment examined the ability of the CCK(A) receptor antagonist devazepide to block the effects of IL-1 and estradiol on food intake in female rats. Adult animals were ovariectomized and given two daily subcutaneous injections of estradiol benzoate (EB; 5.0 microg) or the oil vehicle 3 weeks after surgery. Three days after treatment onset, animals were pretreated with devazepide or its vehicle 30 min prior to intraperitoneal injections of IL-1beta (4.0 microg/kg) or saline given 1 h before light offset. Food and water intake was measured following 2 h of spontaneous feeding. The results indicate that devazepide failed to reverse the anorectic action of IL-1beta, although the effects of estradiol on food intake were blocked by devazepide. These data do not support a role for CCK in IL-1-induced anorexia, and suggest that cytokines may act directly on neural systems involved in the control of food intake.