University of Washington

1

Dutton, R.P., Lee, L.A., Stephens, L.S., Posner, K.L., Davies, J.M., Domino, K.B.: Massive hemorrhage: a report from the Anesthesia Closed Claims Project. Anesthesiology 121:450-8, 2014.

Accompanied by an editorial by Scavone, B.M., Tung, A. The transfusion dilemma: More, less, or more organized? (Anesthesiology 121:439-41, 2014).
Accompanied by an Infographics in Anesthesiology by Wanderer JP, Rathmell JP: Massive hemorrhage and malpractice claims. (Anesthesiology 121: 2014).

Massive hemorrhage represents a high risk to surgical and obstetric anesthesia patients. There have been significant advances in management of perioperative hemorrhage but whether these have been incorporated into clinical practice remains unclear. We analyzed anesthesia malpractice claims associated with massive hemorrhage to identify common factors associated with adverse patient outcome that could guide improvements in management of perioperative hemorrhage.

One surprising finding was the relative overrepresentation of spine, obstetric and laparoscopic/robotic cases in hemorrhage malpractice claims compared to their representation in anesthesia practice as reported in the National Anesthesia Clinical Outcomes Registry (NACOR). As pointed out in the accompanied Infographics analysis by Wanderer and Rathmell, spine, obstetrics and robotic procedures are not commonly associated with large transfusion requirements.

Unique to this study was the finding that massive hemorrhage malpractice claims were commonly associated with delays in diagnosis, transfusion, and return to the OR, as well as lapses in team communication. The accompanying editorial by Scavone and Tung supports the authors recommendations for protocol driven organized responses to diagnosis and treatment of massive perioperative and obstetric hemorrhage.

2

Kassebaum NJ, Bertozzi-Villa A, Coggeshall M, et. al. Global, regional, and national levels and causes of maternal mortality, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet, 2014 Sep 13; 384(9947):980-1004 doi: 10.1016/S0140-6736(14)60696-6

Millennium Development Goal 5 (MDG5) aims for a 75% reduction in maternal mortality ratio (MMR) between 1990 and 2015. To update global progress, we employed robust statistical methods on a database of 7065 site-years, estimating total maternal deaths from 1990 through 2013 for 188 countries. We then performed country-specific disaggregation into nine detailed causes and four time periods using Bayesian meta-regression.

293,000 (261,017 - 327,792) maternal deaths occurred in 2013, down from 376,000 (343,483 - 407,574) in 1990. The global annual rate of change was -0.3% (-1.1% to 0.6%) from 1990 to 2003 and -2.7% (-3.9% to -1.5%) from 2003 to 2013, with evidence of continued acceleration. Regional trends vary dramatically. MMR is highest in older ages, peaking in ages 45-49. Most deaths occur during the intra-partum and post-partum periods. There is significant regional variation in the cause pattern, along with substantial changes in the cause pattern from 1990 to 2013.

Only 16 developing countries are on pace to achieve MDG5. Recently accelerating declines coincide with increased development assistance for health for maternal, newborn and child health. Setting post-2015 targets and associated interventions will require careful consideration of regions that currently are experiencing slower progress including West and Central Africa.

Explore: http://vizhub.healthdata.org/mdg5/

3

Sutton, B. C., and M. R. Opp. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization. SLEEP 37: 515-524, 2014.

http://www.ncbi.nlm.nih.gov/pubmed/24587574

Chronic pain and insufficient sleep independently constitute tremendous public health burdens. Although each is recognized as a public health problem, as co-morbidities they threaten to swamp health care delivery systems, they devastate quality of life, and they cost billions in lost productivity and absenteeism. Bi-directional links exist such that pain disrupts sleep and sleep loss exacerbates pain, yet recent analyses suggest the effect of insufficient sleep on pain may be stronger than that of pain on sleep. Musculoskeletal pain conditions are particularly burdensome because they are the most prevalent in our society, yet little pre-clinical research has focused on the role of sleep disturbance in the etiology of these pain conditions. In this study using a model of muscle pain induced by acidic saline injections, the authors demonstrate that evoked pain symptoms (mechanical allodynia) are exacerbated when sleep of mice is disrupted during the period when muscle pain develops. These effects persist for at least three weeks, the duration of the protocol used in this study. Although mechanisms underlying sleep disruption and exacerbation of pain are largely unknown, this study suggests insufficient sleep may be underappreciated as a contributor to chronic pain.

4

Vavilala MS, Kernic MA, Wang J, Kannan N, Mink RB, Wainwright MS, Groner JI, Bell MJ, Giza CC, Zatzick DF, Ellenbogen RG, Boyle LN, Mitchell PH, Rivara FP; Pediatric Guideline Adherence and Outcomes Study. Acute care clinical indicators associated with discharge outcomes in children with severe traumatic brain injury. Crit Care Med. 2014 Oct;42(10):2258-66.

We tested the relationship between adherence to suggested acute care severe traumatic brain injury (TBI) guidelines and discharge outcomes. Children < 18 years with severe TBI who received ICU care at 5 regional pediatric trauma centers between 2007-2011 were examined. Total adherence rate across all locations and all centers was 68%-78%. Overall adherence was associated with survival (aHR 0.94; 95% CI 0.91-0.96). Three specific indicators were associated with survival: no prehospital hypoxia (aHR 0.20; 95% CI 0.08-0.46), early nutrition ICU start (aHR 0.06; 95% CI 0.01-0.26), and ICU PaCO2 > 30mmHg without cerebral herniation (aHR 0.22; 95% CI 0.06-0.8). Overall adherence was also associated with favorable GOS (aHR 0.99; 95% CI 0.98-0.99). Three indicators were associated with favorable discharge GOS: all operating room cerebral perfusion pressure (CPP) > 40 mmHg (aRR 0.61; 95% CI 0.58-0.64), all ICU CPP > 40 mm Hg (aRR 0.73; 95% CI 0.63-0.84), and no surgery (aRR 0.68; 95% CI 0.53- 0.86). Adherence to the Pediatric Guidelines was associated with significantly higher discharge survival and improved discharge GOS. Some indicators were protective regardless of treatment location, suggesting a benefit for an interdisciplinary approach to severe TBI.

5

Kim M, Hunter RW, Garcia-Menendez L, Gong G, Yang YY, Kolwicz SC Jr, Xu J, Wang W, Sakamoto K, Tian R. Mutation in the g2-subunit of AMPK Stimulates Cardiomyocyte Proliferation and Hypertrophy Independent of Glycogen Storage. Circ Res. 2014 Mar 14;114(6):966-75

AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of cell metabolism. Activation of AMPK during stress conditions protects energy homeostasis by stimulating substrate metabolism for ATP production and by suppression of growth and promotion of autophagy. These functions make AMPK an attractive drug target. Interestingly, point mutations in γ2 regulatory subunit (encoded by Prka2g) caused aberrant AMPK activity and cardiomyopathy with glycogen storage, arrhythmia and excessive cardiac growth in humans. It raises the concern of targeting AMPK for therapy and also the question of isoform-specific function of γ2-AMPK. In a mouse model of N488I mutation of the Prkag2, we rescued the glycogen storage phenotype by genetic inhibition of glucose-6-phosphate stimulated glycogen synthase activity. We show that the mutation of γ2-AMPK, independent of glycogen accumulation in the heart, accentuates insulin signaling, increases cell proliferation during the postnatal growth period and stimulates myocyte hypertrophy in adulthood, leading to abnormal cardiac growth. Inhibition of mTOR activity by rapamycin or restoration of FoxO activity by overexpressing FoxO1 rescued the abnormal cardiac growth. These observations provide new insights to the pathogenesis of Prka2g cardiomyopathy, and further stress the importance of isoform-specific function of AMPK for the pharmacological targeting of the AMPK.