Surgery In Early Life Research Articles

Effects of Early Exposure to Isoflurane on Susceptibility to Chronic Pain Are Mediated by Increased Neural Activity Due to Actions of the Mammalian Target of the Rapamycin Pathway.

Patients who have undergone surgery in early life may be at elevated risk for suffering neuropathic pain in later life. The risk factors for this susceptibility are not fully understood. Here, we used a mouse chronic pain model to test the hypothesis that early exposure to the general anesthetic (GA) Isoflurane causes cellular and molecular alterations in dorsal spinal cord (DSC) and dorsal root ganglion (DRG) that produces a predisposition to neuropathic pain via an upregulation of the mammalian target of the rapamycin (mTOR) signaling pathway. Mice were exposed to isoflurane at postnatal day 7 (P7) and underwent spared nerve injury at P28 which causes chronic pain. Selected groups were treated with rapamycin, an mTOR inhibitor, for eight weeks. Behavioral tests showed that early isoflurane exposure enhanced susceptibility to chronic pain, and rapamycin treatment improved outcomes. Immunohistochemistry, Western blotting, and q-PCR indicated that isoflurane upregulated mTOR expression and neural activity in DSC and DRG. Accompanying upregulation of mTOR and rapamycin-reversible changes in chronic pain-associated markers, including N-cadherin, cAMP response element-binding protein (CREB), purinergic P2Y12 receptor, glial fibrillary acidic protein (GFAP) in DSC; and connexin 43, phospho-extracellular signal-regulated kinase (p-ERK), GFAP, Iba1 in DRG, were observed. We concluded that early GA exposure, at least with isoflurane, alters the development of pain circuits such that mice are subsequently more vulnerable to chronic neuropathic pain states.

A Painful Beginning: Early Life Surgery Produces Long-Term Behavioral Disruption in the Rat.

Early life surgery produces peripheral nociceptive activation, inflammation, and stress. Early life nociceptive input and inflammation have been shown to produce long-term processing changes that are not restricted to the dermatome of injury. Additionally stress has shown long-term effects on anxiety, depression, learning, and maladaptive behaviors including substance abuse disorder and we hypothesized that early life surgery would have long-term effects on theses complex behaviors in later life. In this study surgery in the rat hindpaw was performed to determine if there are long-term effects on anxiety, depression, audiovisual attention, and opioid reward behaviors. Male animals received paw incision surgery and anesthesia or anesthesia alone (sham) at postnatal day 6. At 10 weeks after surgery, open field center zone entries were decreased, a measure of anxiety (n = 20) (P = 0.03) (effect size, Cohen’s d = 0.80). No difference was found in the tail suspension test as a measure of depression. At 16–20 weeks, attentional performance in an operant task was similar between groups at baseline and decreased with audiovisual distraction in both groups (P < 0.001) (effect size, η2 = 0.25), but distraction revealed a persistent impairment in performance in the surgery group (n = 8) (P = 0.04) (effect size, η2 = 0.13). Opioid reward was measured using heroin self-administration at 16–24 weeks. Heroin intake increased over time in both groups during 24-h free access (P < 0.001), but was greater in the surgery group (P = 0.045), with a significant interaction between time and treatment (P < 0.001) (effect size, Cohen f 2 = 0.36). These results demonstrate long-term disruptions in complex behaviors from surgical incision under anesthesia. Future studies to explore sex differences in early life surgery and the attendant peripheral neuronal input, stress, and inflammation will be valuable to understand emerging learning deficits, anxiety, attentional dysfunction, and opioid reward and their mechanisms. This will be valuable to develop optimal approaches to mitigate the long-term effects of surgery in early life.

Surgical Management of Aorto-Ventricular Tunnel. A Multicenter Study

Aorto-ventricular tunnel (AoVT), a rare congenital anomaly, is a channel originating in the ascending aorta just above the sinotubular junction and leading to the cavity of the left ventricle (AoLVT), or, rarely, the right (AoRVT). This study reviews our collective 30-year experience with the surgical treatment of AoVT. Data were submitted by 15 participating centers on 42 patients who underwent correction of AoVT between 1987 and 2018. Of these, 36 had AoLVT, and 6 AoRVT. The tunnel originated above the right coronary sinus in 28 (77.8%) patients. For AoLVT, most operations were performed early (median age 25 days, range: 1 day-25 years). In contrast, AoRVT was diagnosed and repaired later (median age 6 years, range: 1 month-12 years). Surgically important coronary ostial displacement was common. Patch closure of the aortic orifice only was the commonest surgical repair for AoLVT (23 patients), while in AoRVT, both orifices or only the ventricular one was closed. Aortic valvar insufficiency, severe or moderate, coexisted in 11 (30.5%) patients with AoLVT, and aortic valvuloplasty was performed in 8, mainly due to aortic valve stenosis. Aortic valvar insufficiency at discharge ranged from trivial to mild in almost all patients. Early mortality was 7.14%, with 3 patients with AoLVT succumbing to cardiac failure. There were 2 early reoperations and 1 late death. AoVT is a rare malformation. AoLVT usually necessitates surgery in early life. AoRVT is rarer, diagnosed and repaired later in life. Surgical repair by patch closure, with concomitant aortic valve repair as needed, is associated with good results.

Epilepsy Surgery in Early Life: The Earlier, The Better

Epilepsy Surgery in Early Life: The Earlier, The Better

Assessment of Pediatric Cardiology Referral Practices for Inpatient and Outpatient Post-Cardiac Surgery Physical Therapy

Purpose: Congenital heart disease (CHD) occurs in 4-12 per 1,000 live births with more than 30% of affected children requiring palliative or corrective surgery in early life. Studies on adult cardiac surgery patients clearly demonstrate the benefit of physical therapy (PT), a standard postoperative care step. However, it is unknown to what extent pediatric cardiac patients are referred for post-surgical PT in both inpatient and outpatient settings. The objective of this study is to assess pediatric cardiologist (PC) referral practices for both inpatient and outpatient post-cardiac surgery physical …

A Population-based Study Evaluating the Association Between Surgery in Early Life and Child Development at Primary School Entry

(Anesthesiology. 2016;125:272–279) Surgery in childhood warrants the administration of anesthetics or sedatives. Earlier studies have indicated a significant correlation between anesthetic exposure in childhood and neurodevelopment, as evaluated by academic performance indicators or behavioral outcomes. The present population-based cohort study aimed to analyze the impact of anesthesia and surgery in early childhood on child development.

Early Childhood Development of Boys with Genital Anomalies.

Male genital anomalies often require surgery in early life to address functional and cosmetic consequences. However, there has been little assessment of developmental outcomes of affected boys. We conducted a population-based cohort study of all boys born in New South Wales, Australia, and undergoing school-entry developmental assessment in 2009 or 2012. Health and developmental information was obtained by means of record-linkage of birth, hospital and Australian Early Development Census data. Boys with hypospadias or undescended testis (UDT) were compared with those without. Developmental outcomes were assessed in five domains (physical health, emotional maturity, communication, cognitive skills, and social competence), and boys were categorized as vulnerable (<10th centile of national scores), developmentally high risk (DHR; vulnerable in 2+ domains), and special needs. We included 420 boys with hypospadias, 873 with UDT, and 77,176 unaffected boys. There was no difference in the proportion of boys developmentally vulnerable in any domain or DHR between boys with hypospadias (DHR: n = 49; 13.1%; p = 0.9), UDT (n = 116; 15.2%; p = 0.06), and unaffected boys (n = 9278; 12.9%). Compared with unaffected boys (n = 4826; 6.3%), boys with hypospadias (n = 43; 10.2%; p < 0.001) or UDT (n = 105; 12.0%; p < 0.001) were more likely to have special needs. Stratified analyses revealed that only boys with UDT and coexisting anomalies had increased risk of being DHR (odds ratio: 2.65; 95% confidence interval, 1.61-4.36) or special needs (odds ratio: 2.91; 95% confidence interval, 2.00-4.22). We found no increased risk of poor development among boys with hypospadias or UDT. However, boys with UDT and coexisting anomalies were more likely to have poorer development and special needs. Birth Defects Research 109:535-542, 2017. © 2017 Wiley Periodicals, Inc.

A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry.

It is unclear whether exposure to surgery in early life has long-term adverse effects on child development. The authors aimed to investigate whether surgery in early childhood is associated with adverse effects on child development measured at primary school entry. The authors conducted a population-based cohort study in Ontario, Canada, by linking provincial health administrative databases to children's developmental outcomes measured by the Early Development Instrument (EDI). From a cohort of 188,557 children, 28,366 children who underwent surgery before EDI completion (age 5 to 6 yr) were matched to 55,910 unexposed children. The primary outcome was early developmental vulnerability, defined as any domain of the EDI in the lowest tenth percentile of the population. Subgroup analyses were performed based on age at first surgery (less than 2 and greater than or equal to 2 yr) and frequency of surgery. Early developmental vulnerability was increased in the exposed group (7,259/28,366; 25.6%) compared with the unexposed group (13,957/55,910; 25.0%), adjusted odds ratio, 1.05; 95% CI, 1.01 to 1.08. Children aged greater than or equal to 2 yr at the time of first surgery had increased odds of early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% CI, 1.01 to 1.10), but children aged less than 2 yr at the time of first exposure were not at increased risk (odds ratio, 1.04; 95% CI, 0.98 to 1.10). There was no increase in odds of early developmental vulnerability with increasing frequency of exposure. Children who undergo surgery before primary school age are at increased risk of early developmental vulnerability, but the magnitude of the difference between exposed and unexposed children is small.

Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life.

Little is known about chronic neuromotor disability (CND) including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery (CCS). We sought to determine the frequency and presentation of CND in this population while exploring potentially modifiable acute care predictors. This prospective follow-up study included 549 children after CCS requiring cardiopulmonary bypass at ≤6 weeks of age. Groups included those with only 1 CCS, mostly biventricular CHD, and those with >1 CCS, predominantly single ventricle defects. At 4.5 years of age, 420 (94.6%) children received multidisciplinary assessment. Frequency of CND is given as percentage of assessed survivors. Predictors of CND were analyzed using multiple logistic regression analysis. CND occurred in 6% (95% confidence interval [CI] 3.7%-8.2%) of 4.5-year survivors; for 1 CCS, 4.2% (CI 2.3%-6.1%) and >1, 9.8% (CI 7%-12.6%). CND presentation showed: hemiparesis, 72%; spasticity, 80%; ambulation, 72%; intellectual disability, 44%; autism, 16%; epilepsy, 12%; permanent vision and hearing impairment, 12% and 8%, respectively. Overall, 32% of presumed causative events happened before first CCS. Independent odds ratio for CND are age (days) at first CCS, 1.08 (CI 1.04-1.12; P < .001); highest plasma lactate before first CCS (mmol/L), 1.13 (CI 1.03-1.23; P = 0.008); and >1 CCS, 3.57 (CI 1.48-8.9; P = .005). CND is not uncommon among CCS survivors. The frequency of associated disabilities characterized in this study informs pediatricians caring for this vulnerable population. Shortening the waiting period and reducing preoperative plasma lactate levels at first CCS may assist in reducing the frequency of CND.

Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life

Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life

Successful initiation and maintenance of hemodialysis in an adult patient with complete transposition of the great arteries

Cyanotic congenital heart disease (CCHD) is a life-threatening cardiac defect that requires palliative or corrective surgery in early life. Major advances in medical and surgical management have resulted in the survival of CCHD patients to adulthood with or without corrective surgery, though some are at risk of development of end-stage renal disease (ESRD) due to cyanotic nephropathy (CN). There is little or no information on the initiation and maintenance of hemodialysis (HD) in such patients. We present here a case of a 44-year-old man with complete transposition of the great arteries and CN-related ESRD. He had only received a bi-directional Glenn's operation and still suffered persistent severe hypoxemia and impaired cardiac function. ESRD was successfully treated with HD over more than 4years. The case emphasizes the need for special attention in the selection and initiation of renal replacement therapy.

This Month in Anesthesiology

The investigators studied the association between anesthetic exposure before age 4 and the development of learning disabilities (LD) in reading, written language, and mathematics. Educational and medical records of all children born to mothers residing in five townships were examined. A single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79–1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06–2.37, and hazard ratio = 2.60; 95% confidence interval 1.60–4.24, respectively). The authors noted they cannot determine whether anesthesia itself may contribute to LD, or whether the need for multiple anesthetics is a marker for other unidentified factors that contribute to LD.The authors hypothesized that natriuretic peptide system gene variants independently predict risk of ventricular dysfunction (VnD) after primary coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 natriuretic peptide system genes were genotyped. Seven natriuretic SNPs were associated with decreased risk of postoperative VnD (odds ratios = 0.44–0.55; P = 0.010–0.036) and four natriuretic SNPs were associated with increased risk of postoperative VnD (odds ratios = 3.89–4.28; P = 0.007–0.034). Knowledge of natriuretic peptide system gene variants may result in a better understanding of postoperative VnD after primary coronary artery bypass grafting. These variants may also predict those patients at high risk for VnD so that preventative interventions can be explored. See the accompanying Editorial View on page 693 Exposure to anesthetics administered to young animals causes neurohistopathologic changes including apoptosis, a form of programmed cell death. The investigators examined isoflurane-mediated apoptosis in isolated neuronal tissues in vitro. The authors focused their investigation on a precursor of mature brain-derived neurotrophic factor (BDNF), called proBDNF, and its receptor, the p75 neurotrophin receptor (p75NTR). Inhibition of the proBDNF–p75NTRsignaling pathway blocked isoflurane-mediated neuronal apoptosis in cultured neurons from the developing rodent brain. If exposure to anesthesia and surgery in early life impairs neural development, the proBDNF–p75NTRsignaling pathway may be a target for future therapeutic intervention. See the accompanying Editorial View on page 709 The authors examined the association between preoperative executive function, depression, and other established clinical predictors of postoperative delirium among 998 patients undergoing major noncardiac surgery. Patients were screened prospectively using the Confusion Assessment Method as well as by retrospective chart review. Thirty-five patients developed delirium postoperatively (3.5%). Preoperative executive dysfunction (P = 0.007) and greater levels of depression (P = 0.049) were associated with a greater incidence of postoperative delirium. Complex tests for executive function were more strongly associated with postoperative delirium than simpler tests. In the future, preoperative screening of patients at risk for delirium may facilitate testing of preventative interventions.The pursuit of excellence should always be the number one agenda item for all anesthesiologists. See the accompanying Editorial View on page 712 A preoperative screening tool for obstructive sleep apnea and postanesthesia care unit monitoring identified patients at risk for later adverse postoperative respiratory events.Independent predictors of impossible mask ventilation were determined.Keys for safe perioperative airway management of obese patients with obstructive sleep apnea are reviewed.

Interactions between Trabecular Meshwork Cells and Lens Epithelial Cells: A Possible Mechanism in Infantile Aphakic Glaucoma

Infantile aphakic glaucoma may develop as a postoperative complication of early childhood cataract surgery. It has been associated with risk factors including surgery in early life and retained lens material; however, its cause and mechanism are poorly understood. This study focused on the potential role of retained lens material (specifically, exposed lens epithelial cells [LECs]) in undesired changes of the trabecular meshwork (TM) structure and function. Interactions between LECs and TM cells were studied by analyzing structural changes and differential gene and protein expression in TM cells cocultured with LECs. Subjecting normal TM cells to the presence of LECs resulted in changes in their structural features (such as increase in volume and size, and decrease in cell-cell interactions), as well as in their protein expression (mainly cytoskeletal) and gene expression (such as genes related to organ and cell morphogenesis, inflammatory response, response to stimulus, ion homeostasis, and several signaling pathways). Many of the changes observed in TM cells after exposure to LECs resemble alternations seen in primary open-angle glaucoma. This strengthens the suspected role of LECs in the development of aphakic glaucoma.

Thoracic surgery in early life.

Thoracic surgery in early life.