Asha Shenoi

Mitigation of autophagy ameliorates hepatocellular damage following ischemia-reperfusion injury in murine steatotic liver

Ischemia-reperfusion injury (IRI) is a common clinical consequence of hepatic surgery, cardiogenic shock, and liver transplantation. A steatotic liver is particularly vulnerable to IRI, responding with extensive hepatocellular injury. Autophagy, a lysosomal pathway balancing cell survival and cell death, is engaged in IRI, although its role in IRI of a steatotic liver is unclear. The role of autophagy was investigated in high-fat diet (HFD)-fed mice exposed to IRI in vivo and in steatotic hepatocytes exposed to hypoxic IRI (HIRI) in vitro. Two inhibitors of autophagy, 3-methyladenine and bafilomycin A1, protected the steatotic hepatocytes from HIRI. Exendin 4 (Ex4), a glucagon-like peptide 1 analog, also led to suppression of autophagy, as evidenced by decreased autophagy-associated proteins [microtubule-associated protein 1A/1B-light chain 3 (LC3) II, p62, high-mobility group protein B1, beclin-1, and autophagy-related protein 7], reduced hepatocellular damage, and improved mitochondrial structure and function in HFD-fed mice exposed to IRI. Decreased autophagy was further demonstrated by reversal of a punctate pattern of LC3 and decreased autophagic flux after IRI in HFD-fed mice. Under the same conditions, the effects of Ex4 were reversed by the competitive antagonist exendin 9-39. The present study suggests that, in IRI of hepatic steatosis, treatment of hepatocytes with Ex4 mitigates autophagy, ameliorates hepatocellular injury, and preserves mitochondrial integrity. These data suggest that therapies targeting autophagy, by Ex4 treatment in particular, may ameliorate the effects of IRI in highly prevalent steatotic liver.

Refractory Hypotension From Massive Bupropion Overdose Successfully Treated With Extracorporeal Membrane Oxygenation

An 11-month-old male infant presented with history of bupropion ingestion (750 mg/kg). He developed seizures, respiratory failure, and severe hypotension with metabolic acidosis refractory to inotropic support. The patient received mechanical ventilation, intralipids, phenytoin, inotropic support (dopamine, norepinephrine, and epinephrine), and extracorporeal membrane oxygenation (ECMO). Inotropes were weaned upon initiation of ECMO and discontinued 66 hours after ingestion. Total ECMO duration was 71 hours. The patient was extubated on hospital day 8 and has not had any neurological sequelae upon 12-month follow-up examinations. We report for the first time successful use of ECMO after ingestion of a potentially fatal dose of bupropion.

Trend and Outcomes of Video Laryngoscope Use Across Picus.

Objective: Video (indirect) laryngoscopy is used as a primary tracheal intubation device for difficult airways in emergency departments and in adult ICUs. The use and outcomes of video laryngoscopy compared with direct laryngoscopy has not been quantified in PICUs or cardiac ICUs. Design: Retrospective review of prospectively collected observational data from a multicenter tracheal intubation database (National Emergency Airway Registry for Children) from July 2010 to June 2015. Setting: Thirty-six PICUs/cardiac ICUs across the United States, Canada, Japan, New Zealand, and Singapore. Patients: Any patient admitted to a PICU or a pediatric cardiac ICU and undergoing tracheal intubation. Interventions: Use of direct laryngoscopy versus video laryngoscopy for tracheal intubation. Measurements and Main Results: There were 8,875 tracheal intubations reported in the National Emergency Airway Registry for Children database, including 7,947 (89.5%) tracheal intubations performed using direct laryngoscopy and 928 (10.5%) tracheal intubations performed using video laryngoscopy. Wide variability in video laryngoscopy use exists across PICUs (median, 2.6%; range, 0–55%). Video laryngoscopy was more often used in older children (p < 0.001), in children with history of a difficult airway (p = 0.01), in children intubated for ventilatory failure (p < 0.001), and to facilitate the completion of an elective procedure (p = 0.048). After adjusting for patient-level covariates, a secular trend, and site-level variance, the use of video laryngoscopy significantly increased over a 5-year period compared with fiscal year 2011 (odds ratio, 6.7; 95% CI, 1.7–26.8 for fiscal year 2014 and odds ratio, 11.2; 95% CI, 3.2–38.9 for fiscal year 2015). The use of video laryngoscopy was independently associated with a lower occurrence of tracheal intubation adverse events (adjusted odds ratio, 0.57; 95% CI, 0.42–0.77; p < 0.001) but not with a lower occurrence of severe tracheal intubation adverse events (adjusted odds ratio, 0.86; 95% CI, 0.56–1.32; p = 0.49) or fewer multiple attempts at endotracheal intubation (adjusted odds ratio, 0.93; 95% CI, 0.71–1.22; p = 0.59). Conclusions: Using National Emergency Airway Registry for Children data, we described patient-centered adverse outcomes associated with video laryngoscopy compared with direct laryngoscopy for tracheal intubation in the largest reported international cohort of children to date. Data from this study may be used to design sufficiently powered prospective studies comparing patient-centered outcomes for video laryngoscopy versus direct laryngoscopy during endotracheal intubation.

Burnout and Psychological Distress Among Pediatric Critical Care Physicians in the United States

Objectives: To estimate the prevalence of physician burnout, psychological distress, and its association with selected personal and practice characteristics among pediatric critical care physicians and to evaluate the relationship between burnout and psychological distress. Design: Cross-sectional, online survey. Setting: Pediatric critical care practices in the United States. Subjects: Pediatric critical care physicians. Interventions: None. Measurement and Main Results: A nonrandom sample of 253 physicians completed an online survey consisting of personal and practice characteristics, the Maslach Burnout Inventory, and the General Health Questionnaire. Nearly half of the participants (49%; 95% CI, 43–55%; n = 124) scored high burnout in at least one of the three subscales of the Maslach Burnout Inventory and 21% reported severe burnout. The risk of any burnout was about two times more in women physicians (odds ratio, 1.97; 95% CI, 1.2–3.4). Association between other personal or practice characteristics and burnout was not evident in this study, while regular physical exercise appeared to be protective. One third of all participants (30.5%) and 69% of those who experienced severe burnout screened positive for psychological distress. About 90% of the physicians reporting severe burnout have considered leaving their practice. Conclusions: Burnout is high among pediatric critical care physicians in the United States. About two thirds of the physicians with severe burnout met the screening criteria for psychological distress that suggests possible common mental disorders. Significant percentages of physicians experiencing burnout and considering to leave the profession has major implications for the critical care workforce.

Clinical Impact of External Laryngeal Manipulation During Laryngoscopy on Tracheal Intubation Success in Critically Ill Children

Objectives: External laryngeal manipulation is a commonly used maneuver to improve visualization of the glottis during tracheal intubation in children. However, the effectiveness to improve tracheal intubation attempt success rate in the nonanesthesia setting is not clear. The study objective was to evaluate the association between external laryngeal manipulation use and initial tracheal intubation attempt success in PICUs. Design: A retrospective observational study using a multicenter emergency airway quality improvement registry. Setting: Thirty-five PICUs within general and children’s hospitals (29 in the United States, three in Canada, one in Japan, one in Singapore, and one in New Zealand). Patients: Critically ill children (< 18 years) undergoing initial tracheal intubation with direct laryngoscopy in PICUs between July 1, 2010, and December 31, 2015. Measurements and Main Results: Propensity score–matched analysis was performed to evaluate the association between external laryngeal manipulation and initial attempt success while adjusting for underlying differences in patient and clinical care factors: age, obesity, tracheal intubation indications, difficult airway features, provider training level, and neuromuscular blockade use. External laryngeal manipulation was defined as any external force to the neck during laryngoscopy. Of the 7,825 tracheal intubations, the initial tracheal intubation attempt was successful in 1,935/3,274 intubations (59%) with external laryngeal manipulation and 3,086/4,551 (68%) without external laryngeal manipulation (unadjusted odds ratio, 0.69; 95% CI, 0.62–0.75; p < 0.001). In propensity score–matched analysis, external laryngeal manipulation remained associated with lower initial tracheal intubation attempt success (adjusted odds ratio, 0.93; 95% CI, 0.90–0.95; p < 0.001). Conclusions: External laryngeal manipulation during direct laryngoscopy was associated with lower initial tracheal intubation attempt success in critically ill children, even after adjusting for underlying differences in patient factors and provider levels. The indiscriminate use of external laryngeal manipulation cannot be recommended.

Recurrent rhabdomyolysis in a teenager with psychosis-intermittent hyponatremia-polydipsia syndrome.

Objective To report a case of recurrent hyponatremia and rhabdomyolysis in a teenager with psychogenic polydipsia. Case Summary A 16-year-old boy was admitted with recurrent episodes of hyponatremia and rhabdomyolysis secondary to psychogenic polydipsia. He was treated with hypertonic saline, intravenous fluids, and supportive care. Discussion Psychogenic polydipsia is a condition characterized by compulsive drinking. Severe hyponatremia is a rare, but serious complication in patients with psychogenic polydipsia. Failure in cell volume regulatory mechanisms, defective osmoregulation, defective urinary dilution, and enhanced secretion of vasopressin are believed to play a role in the development of hyponatremia. Rhabdomyolysis can complicate severe hyponatremia, although the exact mechanism is not known. Antipsychotic drugs are also implicated in rhabdomyolysis. Conclusions Severe hyponatremia and rhabdomyolysis can complicate psychogenic polydipsia. Patients receiving antipsychotic drugs with concomitant severe hyponatremia need to be monitored for rhabdomyolysis.

Frequency of Desaturation and Association with Hemodynamic Adverse Events during Tracheal Intubations in PICUs

Objectives: Oxygen desaturation during tracheal intubation is known to be associated with adverse ICU outcomes in critically ill children. We aimed to determine the occurrence and severity of desaturation during tracheal intubations and the association with adverse hemodynamic tracheal intubation–associated events. Design: Retrospective cohort study as a part of the National Emergency Airway Registry for Children Network’s quality improvement project from January 2012 to December 2014. Setting: International PICUs. Patients: Critically ill children younger than 18 years undergoing primary tracheal intubations in the ICUs. Interventions: tracheal intubation processes of care and outcomes were prospectively collected using standardized operational definitions. We defined moderate desaturation as oxygen saturation less than 80% and severe desaturation as oxygen saturation less than 70% during tracheal intubation procedures in children with initial oxygen saturation greater than 90% after preoxygenation. Adverse hemodynamic tracheal intubation–associated event was defined as cardiac arrests, hypo or hypertension requiring intervention, and dysrhythmia. Measurements and Main Results: A total of 5,498 primary tracheal intubations from 31 ICUs were reported. Moderate desaturation was observed in 19.3% associated with adverse hemodynamic tracheal intubation–associated events (9.8% among children with moderate desaturation vs 4.4% without desaturation; p < 0.001). Severe desaturation was observed in 12.9% of tracheal intubations, also significantly associated with hemodynamic tracheal intubation–associated events. After adjusting for patient, provider, and practice factors, the occurrence of moderate desaturation was independently associated with hemodynamic tracheal intubation–associated events: adjusted odds ratio 1.83 (95% CI, 1.34–2.51; p < 0.001). The occurrence of severe desaturation was also independently associated with hemodynamic tracheal intubation–associated events: adjusted odds ratio 2.16 (95% CI, 1.54–3.04; p < 0.001). Number of tracheal intubation attempts was also significantly associated with the frequency of moderate and severe desaturations (p < 0.001). Conclusions: In this large tracheal intubation quality improvement database, we found moderate and severe desaturation are reported among 19% and 13% of all tracheal intubation encounters. Moderate and severe desaturations were independently associated with the occurrence of adverse hemodynamic events. Future quality improvement interventions may focus to reduce desaturation events.

Teaching the Principles of Pediatric Critical Care to Non-Intensivists in Resource Limited Settings: Challenges and Opportunities

It is a dismal reality of global health that the vast majority of critically ill or injured children are found in regions of the world least equipped to care for them. Most of these severely ill or injured children are cared for in clinics, hospital wards, or, when available, adult intensive care units (ICUs) by providers with variable amounts of training. This lack of training may, in fact, play a significant role in the premature demise of children <5 years old, since millions of these deaths are felt to be preventable with the resources available (1). Evidence shows that even in a setting with constrained resources, early recognition, and prompt, decisive intervention may reduce mortality (2–4). It seems intuitive, therefore, that training of non-intensivists that focuses on these principles might improve the outcomes in critically ill children. How can this instruction be best achieved in areas where it is most needed? In this article, we review the benefits and challenges of implementing short-term curricula to teach the basic principles and practice of critical care medicine in resource limited settings (RLS).

1286: BURNOUT AMONG PEDIATRIC INTENSIVE CARE ADVANCED PRACTICE PROVIDERS IN THE UNITED STATES

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Burnout syndrome (BOS) is common among critical care nurses and physicians. Prevalence of BOS among pediatric critical care physicians exceeds that of other physicians. Data on the prevalence of BOS in pediatric intensive care advanced practice providers (nurse practitioners and physician assistants) is lacking. We sought to assess the prevalence of and factors associated with BOS among pediatric intensive care advanced practice providers (APPs) in the United States. Methods: We conducted a cross-sectional survey of pediatric intensive care APPs in the U.S. using the online platform Qualtrics. Information on demographics and practice settings was collected. BOS was assessed using a modified Maslach Burnout Inventory, and categorized as high, moderate, or low in the domain of emotional exhaustion. Themes assessed included autonomy of APPs, communication with physicians, organizational and unit practices, perceived work-life balance, and amount and perceived quality of sleep. Results: Sixty-one responses were received. The response rate cannot be calculated because the exact number of APPs in pediatric intensive care settings in the U.S. is unknown. Responders were widely geographically distributed across the U.S., were predominantly female, and most were married or in a committed relationship. Over 75% practice in academic settings, 58% practice in free-standing children’s hospitals, and 46% practice in general medical-surgical PICUs. Almost two-thirds of participants scored high levels of burnout in the emotional exhaustion domain. Statistically significant relationships were found between emotional exhaustion scores and perceived level of work-life balance (p = .010), perceived quality of sleep (p = .046), and organizational assistance with development of coping mechanisms (p = 0.12). Conclusions: This study identified a high prevalence of burnout among pediatric intensive care APPs. High rates of burnout were related to perceived work-life imbalance and poor perceived quality of sleep. Organizational support for development of coping mechanisms was associated with lower burnout scores.

Effect of Location on Tracheal Intubation Safety in Cardiac Disease—Are Cardiac ICUs Safer?

Objectives: Evaluate differences in tracheal intubation–associated events and process variances (i.e., multiple intubation attempts and oxygen desaturation) between pediatric cardiac ICUs and noncardiac PICUs in children with underlying cardiac disease. Design: Retrospective cohort study using a multicenter tracheal intubation quality improvement database (National Emergency Airway Registry for Children). Setting: Thirty-six PICUs (five cardiac ICUs, 31 noncardiac ICUs) from July 2012 to March 2016. Patients: Children with medical or surgical cardiac disease who underwent intubation in an ICU. Interventions: None. Measurements and Main Results: Our primary outcome was the rate of any adverse tracheal intubation–associated event. Secondary outcomes were severe tracheal intubation–associated events, multiple tracheal intubation attempt rates, and oxygen desaturation. There were 1,502 tracheal intubations in children with underlying cardiac disease (751 in cardiac ICUs, 751 in noncardiac ICUs) reported. Cardiac ICUs and noncardiac ICUs had similar proportions of patients with surgical cardiac disease. Patients undergoing intubation in cardiac ICUs were younger (median age, 1 mo [interquartile range, 0–6 mo]) compared with noncardiac ICUs (median 3 mo [interquartile range, 1–11 mo]; p < 0.001). Tracheal intubation–associated event rates were not different between cardiac ICUs and noncardiac ICUs (16% vs 19%; adjusted odds ratio, 0.74; 95% CI, 0.54–1.02; p = 0.069). However, in a sensitivity analysis comparing cardiac ICUs with mixed ICUs (i.e., ICUs caring for children with either general pediatric or cardiac diseases), cardiac ICUs had decreased odds of adverse events (adjusted odds ratio, 0.71; 95% CI, 0.52–0.97; p = 0.033). Rates of severe tracheal intubation–associated events and multiple attempts were similar. Desaturations occurred more often during intubation in cardiac ICUs (adjusted odds ratio, 1.61; 95% CI, 1.04–1.15; p = 0.002). Conclusions: In children with underlying cardiac disease, rates of adverse tracheal intubation–associated events were not lower in cardiac ICUs as compared to noncardiac ICUs, even after adjusting for differences in patient characteristics and care models.