2 Minute Medicine Rewind March 25, 2019

Epidemiology of brain death in pediatric intensive care units in the United States

In the United States, brain death is exclusively diagnosed in critical care settings, owing to the need for mechanical ventilatory support. With ongoing controversy surrounding the definition of brain death in medical, legal and ethical circles, there is a need to improve public trust in the brain death determination process; part of this involves improving our understanding of the contemporary epidemiology of brain death in children in the US. In this national database study of 15,344 patients who died in pediatric intensive care units (PICUs), data on patient deaths were abstracted to characterize the epidemiology and clinical characteristics of pediatric patients declared brain dead in the US (2012-2017). Researchers found that of those patients who had died, 20.7% had been declared brain dead. The most common causative mechanisms of death included hypoxic-ischemic injury secondary to cardiac arrest (52.7%), shock and/or respiratory arrest without cardiac arrest (12.6%) and traumatic brain injury (20.0%). Patients declared brain dead were more likely than those with cardiovascular death to have sustained trauma (40.5% vs. 11.1%, p<0.001) and more likely to have a higher severity of illness (Pediatric Index of Mortality score) at PICU admission) (p <0 .001). The majority of patients declared to be brain dead did not have a pre-existing neurologic condition (84.4%). The medical length of stay was shortest for patients declared brain dead owing to traumatic brain injury (median 2.0 days, IQR 1.3 to 3.6] days, p<0.001). This study therefore showed that brain death occurred in at least 20% of PICU deaths, with most resulting from acute hypoxic-ischemic or traumatic brain injury. Physician education, standardization of brain death protocols, and the use of precise, consistent language are important to ensure the integrity of brain death determination.

Nationwide analysis of resuscitative endovascular balloon occlusion of the aorta in civilian trauma

Massive hemorrhage secondary to traumatic injury continues to be a leading cause of morbidity and mortality. While the use of temporary hemostatic measures including aortic occlusion is not novel, resuscitative endovascular balloon occlusion of the aorta (REBOA) is not routinely used in trauma settings. Prior studies have shown mixed results with respect to its utility in decreasing mortality. In this case-control study, data from the 2015-2016 American College of Surgeons (ACS) Trauma Quality Improvement Program was used to evaluate outcomes in 420 trauma patients that had received REBOA, compared to 280 matched trauma patients that did not receive REBOA. Patients that received REBOA were younger (mean age 44 vs. 53, p=0.88) and more likely to be non-white (p=0.003). In comparing matched patients, there was no difference between the REBOA and no-REBOA groups in terms of age (p=0.88), sex (p=0.76), race, mean systolic blood pressure (SBP) (p=0.65), mean heart rate (p=0.74), median GCS score (p=0.88), mechanism of injury, incidence or type of pelvic fracture (p=0.65), lower limb fractures (p=0.69), vascular injuries (p=0.11), solid organ injury or severity of solid organ injury.

Compared with patients in the no-REBOA group, patients in the REBOA group had a higher 24-hour mortality rate (26.4% vs. 33 11.8%, p=0.01), as well as higher rates of acute kidney injury (10.7% vs. 3.2%, p=0.02) and amputation of a lower limb (3.6% vs. 0.7%, p=0.04). However, there was no significant difference in ED mortality (p=0.35) or mortality after 24 hours (p=0.21), between the REBOA and no-REBOA groups. Moreover, there was no difference between groups in 4-hour or 24-hour blood transfusion requirements for packed red blood cells (PRBCs), platelets, or plasma, and no significant difference in hospital or intensive care unit (ICU) length of stay. All the patients who survived in the emergency room received intervention for definitive hemorrhage control with either angioembolization or exploratory laparotomy. There was no difference between groups in terms of the rate of angioembolization (p=0.18) or exploratory laparotomy (p=0.33). However, the median time from emergency department presentation to angioembolization or exploratory laparotomy was higher in the REBOA group (p=0.04 for both).  This study therefore shows that placement of REBOA in severely injured trauma patients may be associated with a higher mortality rate compared to matched patients managed without placement of REBOA. Patients receiving REBOA may also have higher rates of acute kidney injury and lower leg amputations, further questioning the utility of this modality in trauma settings.

The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study

Previous observational studies have supported a causal link between cannabis use and psychotic disorder. A recent meta-analysis has also shown a dose-response association with the highest odds of psychotic disorder in those with the heaviest cannabis use. It is not clear, however, whether patterns of cannabis use on a population level influence rates of psychotic disorder. This is of increasing significance as a number of countries have now legalized or decriminalized cannabis use, raising concerns that this may lead to an increase in cannabis use and associated harms. In this multi-centre case-control study, 901 adults with a first episode of psychosis presenting to mental health services between May 2010 and April 2015 at one of 17 areas in England, France, the Netherlands, Italy, Spain, and Brazil were studied and compared to 1237 recruited controls to estimate which patterns of cannabis use carry the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of tetrahydrocannabinol (THC) in different types of cannabis available across the sites, the types of cannabis used by participants were stratified in terms of potency, with low potency being defined as strains with THC<10% and high potency exceeding that cut-off, THC≥10%. Compared to controls, cases were younger, more likely to be male, and from ethnic minorities. Controls were more likely to have pursued higher education (p<0.0001) and to have been employed a year before assessment than cases (p<0.0001). Researchers found that more cases than controls reported having ever used cannabis (p<0.001), having smoked ten tobacco cigarettes or more a day (p<0.0001), or having tried other recreational drugs, including legal highs (p=0.0142), stimulants (p<0.0001), hallucinogens (p<0.0001) and ketamine (p=0.0002). Based on the results of an adjusted logistic regression analysis, researchers noted a modest increase in the odds of psychotic disorder compared with those who had never used cannabis (OR 1.3, 95% CI 1.1 to 1.6). The odds were slightly greater in those who started to use cannabis at age 15 years or younger (OR 1.6, 95% CI 1.1 to 2.1). Daily cannabis use was also associated with increased odds of psychotic disorder compared with having never having used it (OR 3.2, 95% CI 2.2 to 4.1). Use of high-potency cannabis (THC ≥10%) modestly increased the odds of a psychotic disorder compared with never use (OR 1.6, 95% CI 1.2 to 2.2); this remained largely unchanged after controlling for daily use (OR 1.5, 95% CI 1.1 to 2.6). Those who had started using high-potency cannabis by age 15 years demonstrated a further doubling of risk, without evidence of interaction (p=0.63). This study therefore shows that daily use of cannabis and use of high-potency cannabis may be important predictors, and possible contributors in the incidence of psychotic disorder. Given the increasing availability of high-potency cannabis, this has important implications for population-based public health initiatives in harm reduction.

Rates of extreme neonatal hyperbilirubinemia and kernicterus in children and adherence to national guidelines for screening, diagnosis, and treatment in Sweden

Neonatal hyperbilirubinemia, left untreated, may lead to lifelong neurodevelopmental impairment. Fortunately, effective tools in risk assessment, prevention, diagnosis and treatment exist, making this a very preventable condition. Despite this, however, cases of kernicterus do occur in high-resource settings. In this population-based nation-wide cohort study, data on the highest serum bilirubin level for all infants born alive at 35 weeks gestation or greater admitted for neonatal care in Sweden (2008-2016) was used to determine incidence rates of hazardous hyperbilirubinemia and kernicterus in this patient population, and to evaluate adherence to best practices. Among 992,378 live-born infants for which data was available, 494 infants developed extreme hyperbilirubinemia (serum bilirubin levels 25.0-29.9 mg/dL or 425-509 μmol/L). The incidence of hazardous hyperbilirubinemia (serum bilirubin levels ³30.0 mg/dL or ³510 μmol/L) and kernicterus was 6.8 per 100,000 infants and 1.3 per 100,000 infants, respectively. Among the 13 children in the study that developed kernicterus, brain injury was assessed as being potentially avoidable for 11 children. This was on the basis of the presence of 1 or several of the following possible causes, including untimely or lack of pre-discharge bilirubin screening (n= 6), misinterpretation of bilirubin values (n= 2), untimely or delayed initiation of treatment with intensive phototherapy (n=1), untimely or no treatment with exchange transfusion (n= 6), or lack of repeated exchange transfusions despite indication (n = 1). This study therefore demonstrates that hazardous hyperbilirubinemia in near-term or term newborns still occurs in high-resource settings. In cases where this leads to disabling neurodevelopmental impairment, non-compliance with best practices is often identified as a contributor. While the incidence is low, this has important implications for improving adherence to best practice guidelines.

Long-term outcome of surgery versus conservative management for recurrent and ongoing complaints after an episode of diverticulitis: 5-year follow-up results of a multicenter randomized controlled trial (DIRECT-Trial)

Roughly 20% of patients affected by diverticulitis experience recurrent symptoms after being treated conservatively, without surgery. This is complicated by the fact that persistent symptoms of diverticulitis can be difficult to distinguish from other conditions such as irritable bowel syndrome (IBS), a functional condition. The DIRECT trial (n=109) compared the effect of elective sigmoidectomy on quality of life (QOL) in patients with recurrent diverticulitis and/or ongoing complaints to conservative treatment in a randomized fashion. Although the study was prematurely terminated due to issues with patient accrual, this trial demonstrated a significantly higher QOL at 6 months of follow-up after elective sigmoidectomy as compared to conservative management. The aim of this study was to evaluate and compare QOL at 5 years of follow-up. QOL was measured using the Gastrointestinal Quality of Life Index (GIQLI). Researchers found that at 5 years of follow-up the mean GIQLI score was significantly higher in the operative group (mean difference 9.7, 95% CI 1.7 to 17.7). Secondary QOL outcomes were also significantly better in the operative group, as assessed using the SF-36 physical (p=0.030) and mental score (p=0.010), Visual Analogue Score (VAS) pain score (p=0.011) and EQ5D score (p=0.016). Furthermore 26% of patients in the conservative group ultimately required surgery due to severe ongoing complaints. Of those treated operatively, 11% experienced anastomotic leakage and reinterventions were required in 15% of patients. This study therefore shows that elective sigmoidectomy results in significantly increased long-term QOL at 5 years of follow-up compared with conservative management in patients with recurring diverticulitis and/or ongoing complaints.

Image: PD

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