Katarina Bojanić

Attention-Deficit/Hyperactivity Disorder After Early Exposure to Procedures Requiring General Anesthesia

OBJECTIVE To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention-deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions. RESULTS Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD. CONCLUSION Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities.

Anesthetic considerations in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome: a case series.

PurposeMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) is a rare inherited mitochondrial disorder associated with severe multiorgan pathology and stress-induced episodes of metabolic decompensation and lactic acidosis. The purpose of this case series is to review the medical records of patients with MELAS who underwent anesthetic care at the Mayo Clinic to observe their perioperative responses to anesthesia and to assess outcomes.Principal findingsFrom September 1997 to October 2010, nine patients with MELAS were identified who underwent 20 general anesthetics, 12 prior to MELAS diagnosis. Debilitating neurologic symptoms involved eight patients, and three patients had substantial cardiac comorbidities. The patients tolerated commonly used anesthetics and muscle relaxants, including succinylcholine. Lactated Ringer’s solution was used frequently. One patient was noted to have elevated postoperative serum lactate, but his serum lactate was chronically elevated. Metabolic acidosis was not observed in any patient. Hyponatremia and hyperkalemia, sometimes profound, were observed in seven patients, but these abnormalities also occurred at times remote from surgery. Two patients developed renal dysfunction following cardiac surgery and abdominal surgery for severe sepsis.ConclusionThe MELAS patients developed episodes of hyponatremia and hyperkalemia of variable severity unrelated to the timing of surgery, suggesting these patients are prone to major electrolyte disturbances. Given the propensity to develop acid-base disturbances and lactacidemia, it is prudent to review and normalize electrolyte abnormalities and to adjust the anesthetic plan accordingly. Fortunately, the limited data suggest that patients with MELAS tolerate commonly used anesthetic drugs well.RésuméObjectifL’encéphalomyopathie mitochondriale avec acidose lactique et épisodes ressemblant à des accidents vasculaires cérébraux (MELAS) est un trouble mitochondrial héréditaire rare associé à une pathologie grave touchant plusieurs organes et des épisodes de décompensation métabolique et d’acidose lactique provoqués par le stress. L’objectif de cette série de cas est d’examiner les dossiers médicaux de patients atteints de MELAS et ayant reçu des soins anesthésiques à la Clinique Mayo afin d’observer leurs réponses périopératoires à l’anesthésie et d’évaluer leurs devenirs.Constatations principalesPour la période allant de septembre 1997 à octobre 2010, nous avons identifié neuf patients atteints de MELAS ayant subi 20 anesthésies générales, dont 12 avant que le diagnostic de MELAS n’ait été établi. Les symptômes neurologiques débilitants ont touché huit patients, et trois patients ont manifesté des comorbités cardiaques importantes. Les patients ont toléré les anesthésiques couramment utilisés et les curares, y compris la succinylcholine. Une solution de lactate Ringer a été fréquemment utilisée. Chez un patient, un lactate sérique postopératoire élevé a été noté, mais son lactate sérique était chroniquement élevé. L’acidose métabolique n’a été observée chez aucun patient. Chez sept patients, on a observé de l’hyponatrémie et de l’hyperkalémie, parfois profondes, mais ces anomalies sont également survenues à des moments éloignés de la chirurgie. Deux patients ont manifesté une dysfonction rénale à la suite d’une chirurgie cardiaque et d’une chirurgie abdominale pour sepsis grave.ConclusionLes patients atteints de MELAS ont manifesté des épisodes d’hyponatrémie et d’hyperkalémie plus ou moins graves et non liés temporellement à la chirurgie, ce qui indique que ces patients sont enclins à subir des perturbations électrolytiques majeures. Étant donné leur propension à manifester des perturbations acido-basiques et une lactacidémie, il est prudent de vérifier et de normaliser les anomalies électrolytiques ainsi que d’adapter le plan anesthésique en conséquence. Heureusement, les données limitées dont nous disposons indiquent que les patients atteints de MELAS tolèrent bien les médicaments anesthésiques couramment utilisés.

Anesthesia and Duchenne or Becker muscular dystrophy: review of 117 anesthetic exposures.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are associated with life‐threatening perioperative complications, including rhabdomyolysis, hyperkalemia, and hyperthermia. Current recommendations contraindicate use of succinylcholine and volatile anesthetics; however, the latter recommendation remains controversial.

Survival of outborns with congenital diaphragmatic hernia: the role of protective ventilation, early presentation and transport distance: a retrospective cohort study

BackgroundCongenital diaphragmatic hernia (CDH) is a congenital malformation associated with life-threatening pulmonary dysfunction and high neonatal mortality. Outcomes are improved with protective ventilation, less severe pulmonary pathology, and the proximity of the treating center to the site of delivery. The major CDH treatment center in Croatia lacks a maternity ward, thus all CDH patients are transferred from local Zagreb hospitals or remote areas (outborns). In 2000 this center adopted protective ventilation for CDH management. In the present study we assess the roles of protective ventilation, transport distance, and severity of pulmonary pathology on survival of neonates with CDH.MethodsThe study was divided into Epoch I, (1990–1999, traditional ventilation to achieve normocapnia), and Epoch II, (2000–2014, protective ventilation with permissive hypercapnia). Patients were categorized by transfer distance (local hospital or remote locations) and by acuity of respiratory distress after delivery (early presentation-occurring at birth, or late presentation, ≥6 h after delivery). Survival between epochs, types of transfers, and acuity of presentation were assessed. An additional analysis was assessed for the potential association between survival and end-capillary blood CO2 (PcCO2), an indirect measure of pulmonary pathology.ResultsThere were 83 neonates, 26 in Epoch I, and 57 in Epoch II. In Epoch I 11 patients (42 %) survived, and in Epoch II 38 (67 %) (P = 0.039). Survival with early presentation (N = 63) was 48 % and with late presentation 95 % (P <0.001). Among early presentation, survival was higher in Epoch II vs. Epoch I (57 % vs. 26 %, P = 0.031). From multiple logistic regression analysis restricted to neonates with early presentation and adjusting for severity of disease, survival was improved in Epoch II (OR 4.8, 95%CI 1.3–18.0, P = 0.019). Survival was unrelated to distance of transfer but improved with lower partial pressure of PcCO2 on admission (OR 1.16, 95%CI 1.01–1.33 per 5 mmHg decrease, P = 0.031).ConclusionsThe introduction of protective ventilation was associated with improved survival in neonates with early presentation. Survival did not differ between local and remote transfers, but primarily depended on severity of pulmonary pathology as inferred from admission capillary PcCO2.

Anesthesia and patients with congenital hyposensitivity to pain.

Background:Congenital hyposensitivity to pain or hereditary sensory and autonomic neuropathy represents a variety of disorders characterized by decreased perception of nociception, loss of other modalities of sensation, and variable expression of autonomic dysfunction. Sensory loss, especially that of pain, is associated with self-mutilations that may require frequent operations. Little is known about the safety of anesthesia for these patients. Methods:The authors performed a computerized search of the Mayo Clinic medical records database between January 1996 and November 2005 for patients with congenital hyposensitivity to pain and related disorders who underwent general anesthesia. Medical records were reviewed for demographics, anesthetic techniques and agents, use of opioids, and perioperative complications. In addition, the authors conducted a comprehensive review of the literature to summarize the current knowledge regarding anesthesia for patients with congenital hyposensitivity to pain, and compared it with the patients with hyposensitivity to pain identified at the Mayo Clinic. Results:The authors identified seven patients with hereditary sensory and autonomic neuropathy II, IV, or V and undefined variants of congenital pain hyposensitivity who generated 17 anesthesia records: 12 for orthopedic operations, 3 for sural nerve biopsies, and 2 for ophthalmologic procedures. In all patients, standard doses of volatile agents were used during anesthesia. Small amounts of opioids were used during the course of eight operations. Most patients experienced mild hypothermia (lowest temperature 34.7°C), and none experienced hyperthermia. All patients were hemodynamically stable during otherwise uneventful anesthesia. During recovery from anesthesia, opioids were given to only one patient, a single dose of 1 mg morphine. Even after major orthopedic operations, the patient did not require additional analgesia. Conclusions:The patients with profound congenital hyposensitivity to pain underwent anesthesia without any adverse events. The authors found that despite reduced pain perception, the requirements for volatile anesthetics were within the expected range for population with normal pain perception, but they did not require opioids postoperatively. Intraoperative mild hypothermia was easily managed by adjustment of environmental temperature.

Malformations associated with congenital diaphragmatic hernia: Impact on survival

BACKGROUND/PURPOSE Congenital diaphragmatic hernia (CDH) is associated with high mortality. Survival is influenced by the extent of pulmonary hypoplasia and additional congenital defects. The purpose of this study was to assess the association of congenital anomalies and admission capillary carbon dioxide levels (PcCO2), as a measure of extent of pulmonary hypoplasia, on survival in neonates with CDH. METHODS This is a retrospective review of neonates with CDH admitted to a tertiary neonatal intensive care unit between 1990 and 2014. Logistic regression was used to assess whether hospital survival was associated with admission PcCO2 or associated anomalies (isolated CDH, CDH with cardiovascular anomalies, and CDH with noncardiac anomalies). The probabilities of survival (POS) score, based on birth weight and 5-min Apgar as defined by the Congenital Diaphragmatic Hernia Study Group were included as a covariate. RESULTS Of 97 patients, 55 had additional malformations (cardiovascular n=12, noncardiac anomalies n=43). POS was lower in CDH with other anomalies compared to isolated CDH. Survival rate was 61.9%, 53.5% and 41.7% in isolated CDH, CDH with noncardiac anomalies and CDH with cardiovascular anomalies, respectively. After adjusting for POS score the likelihood of survival in CDH groups with additional anomalies was similar to isolated CDH (OR 0.95, 95% CI 0.22-4.15, and 1.10, 0.39-3.08, for CDH with and without cardiovascular anomalies, respectively). After adjusting for POS score, lower PcCO2 levels (OR=1.25 per 5mmHg decrease, P=0.003) were associated with better survival. CONCLUSIONS Neonates with CDH have a high prevalence of congenital malformations. However, after adjusting for POS score the presence of additional anomalies was not associated with survival. The POS score and admission PcCO2 were important prognosticating factors for survival.

Congenital diaphragmatic hernia: outcomes of neonates treated at Mayo Clinic with and without extracorporeal membrane oxygenation

Congenital diaphragmatic hernia (CDH) is a rare anomaly with high mortality and long‐term comorbid conditions.

Cardiopulmonary exercise performance is reduced in congenital diaphragmatic hernia survivors

Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia. CDH survivors may have pulmonary morbidity that can decrease cardiopulmonary exercise. We aimed to examine whether cardiopulmonary exercise testing (CPET) results differ in CDH survivors versus healthy age‐matched controls and whether CPET results among CDH survivors differ according to self‐reported daily activity.

Neurocognitive outcomes in congenital diaphragmatic hernia survivors: a cross-sectional prospective study.

BACKGROUND/PURPOSE Congenital diaphragmatic hernia (CDH) survivors may have persistent neurocognitive delays. We assessed neurodevelopmental outcomes in CDH survivors from infancy to late teenage years. METHODS A cross-sectional study was conducted on 37 CDH survivors to examine neurocognitive functioning. Overall cognitive score was tested with the early learning composite (ELC) of Mullen Scales of Early Learning (n=19), and Full Scale IQ (FSIQ) of Wechsler Intelligence Scale for Children-Fourth Edition (n=18). RESULTS ELC was 85.7±16.4, lower than the expected norm of 100, P=0.004, and 6 survivors had moderate, and 3 severe delay, which is not greater than expected in the general population (P=0.148). FSIQ was 99.6±19.1, consistent with the expected norm of 100, P=0.922, and 3 survivors had moderate and 2 severe delay, which is greater than expected (P=0.048). Although ELC was lower than FSIQ (P=0.024), within each testing group overall cognitive ability was not associated with participant age (ELC, P=0.732; FSIQ, P=0.909). Longer hospital stay was the only factor found to be consistently associated with a worse cognitive score across all participants in our cohort. CONCLUSIONS A high percentage of survivors with CDH have moderate to severe cognitive impairment suggesting that these subjects warrant early testing with implementation of therapeutic and educational interventions.

Brain drain: final year medical students’ intentions of training abroad

Background In Croatia, a new European Union (EU) member state since July 2013, there is already a shortage of around 3280 doctors to reach the European average. Objectives To investigate the emigration intentions of the current cohort of final year medical students at Zabreb School of Medicine. Methods An electronic questionnaire was used in June 2013 to assess the attitudes of 232 final year medical students towards working conditions abroad and expectations for career opportunities in Croatia following accession to the EU. Results With an overall response rate of 87%, more than half of the surveyed students (106/202, 53%) intended to travel abroad, either for specialty (52/202, 26%) or subspecialty (54/202, 27%) training. More female students (58/135, 43%) than male students (17/62, 27%) indicated they would not emigrate. Most attractive emigration destinations were: Germany (34/121, 28%), USA (19/121, 16%), the UK (19/121, 16%), Switzerland (16/121, 13%) and Canada (11/121, 9%). The most important goals that respondents aimed to achieve through training abroad were to excel professionally (45/120, 38%), to prosper financially (20/120, 17%) and to acquire new experiences and international exposure (31/120, 26%). Conclusions Students’ motivating factors, goals for and positive beliefs about training abroad, as well as negative expectations regarding career opportunities in Croatia, may point towards actions that could be taken to help make Croatia a country that facilitates medical education and professional career development of young doctors.