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Surveying the Literature: Synopsis of Recent Key Publications

Hessel, Eugene A. II MD

doi: 10.1213/ANE.0000000000001548
Surveying the Literature: Surveying the Literature

From the Department of Anesthesiology, University of Kentucky College of Medicine, Lexington, Kentucky.

Accepted for publication July 6, 2016.

The author declares no conflict of interest.

Address correspondence to Eugene A. Hessel, II, MD, Department of Anesthesiology, University of Kentucky College of Medicine, 800 Rose St, Lexington, KY 40536. Address e-mail to

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Sun LS, Li G, Miller TL, Salorio C, et al. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA. 2016;315:2312–2320.

The investigation continues of the clinical relevance of some preclinical and observational studies suggesting adverse effects of anesthesia on the developing brain. This multicenter pediatric anesthesia neurodevelopmental assessment (PANDA) study compared the neuropsychological function and behavior of 105 American Society of Anesthesiologists (ASA) physical status (PS) 1 or 2 matched sibling pairs 8 to 15 years of age, half of whom had undergone a single general anesthetic before 36 months of age for inguinal hernia repair. No difference was found either in mean IQ scores or in domain- specific neurocognitive function or behavior. Like the preliminary findings of the General Anesthesia compared with Spinal anesthesia (GAS) trial,1 the PANDA results are reassuring, but because of the innate limitations of the study, further studies are required.

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Davidson AJ, Disma N, de Graaff JC, et al. Neuro developmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387:239–250.

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Nagao K, Nonogi H, Yonemoto N, et al. Duration of prehospital resuscitation efforts after out-of-hospital cardiac arrest. Circulation. 2016;133:1386–1396.

When it is acceptable to stop resuscitation after cardiac arrest remains a clinical dilemma. In Japan, emergency medical service (EMS) responders are required to continue the resuscitation efforts for Out of Hospital Cardiac Arrest (OHCA) until return of spontaneous circulation (ROSC) or hospital arrival. This provided the unique opportunity to determine the duration of CPR beyond which 30-day good neurological outcome is unlikely (99%) in 282,183 adult patients with bystander-witnessed OHCA. To achieve a 99% sensitivity for favorable outcome, prehospital resuscitation had to be maintained for 40 minutes from the time of the call to EMS and after 33 minutes of EMS resuscitation (negative predictive value of 98%). The editorial by Mutter and Abella (Circulation. 2016; 133:1338–1340) put these observations in perspective. Similar detailed data are lacking for in-hospital cardiac arrest, but they suggest that resuscitation beyond 30 minutes can be associated with good neurological outcome.1

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Goldberger ZD, Chan PS, Berg RA, et al. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet. 2012;380:1473–1481.

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Jones DS, Grady C, Lederer SE. “Ethics and clinical research”—the 50th anniversary of Beecher’s bombshell. N Engl J Med. 2016;374:2393–2398.

Stark L. The unintended ethics of Henry K. Beecher. Lancet. 2016;387:2374–2375.

Henry Beecher is perhaps better known to the anesthesia community for his early study with Todd of deaths associated with anesthesia. However, in these brief reviews, Jones et al and Stark highlight Beecher’s landmark article published 50 years ago,1 which called attention to breeches in ethical conduct in 22 clinical research studies: what these authors refer to as a bombshell. In the fascinating brief review by Jones et al of the history of ethical guidelines for the conduct of clinical research, the authors outline the previous history and what led to the publication of Beecher’s article. Jones et al and Stark discuss the consequences, some unintended, of Beecher’s article and how this history may affect and guide ethical human subject research in the 21st century.

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Beecher HK. Ethics and clinical research. NEJM. 1966;274:1354–1360.

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Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 201;374:1911–1921.

Postoperative atrial fibrillation is especially common after cardiac and thoracic surgery. It remains unclear whether hemodynamically stable patients with this complication should be treated with the goal of rate control or rhythm control. In this prospective randomized study of 523 patients, no difference was found between these 2 approaches in terms of hospital days, discharge without atrial fibrillation, mortality, or the rate of other serious adverse events. In his accompanying editorial, Calkins (NEJM. 2016;374:1977–1978) concluded that these results suggest that rate control should be the initial approach to these patients, but that further investigation of approaches to minimize the relative high rate of stroke or transient ischemic attack (1.1%) in both groups is needed.

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Holcomb CN, Hollis RH, Graham LA, et al. Association of coronary stent indication with postoperative outcomes following noncardiac surgery. JAMA Surg. 201;151:462–469.

Holcomb CN, Graham LA, Richman JS, et al. The incremental risk of coronary stents on postoperative adverse events: a matched cohort study. Ann Surg. 2016;263:924–930.

The risk of major adverse cardiac events (MACE) after surgery in patients with coronary stents remains a major concern of surgeons and anesthesiologists. In a retrospective study of more than 26,000 patients undergoing surgical procedures in US Veterans Affairs Hospitals within 24 months of coronary stent placement, Holcomb et al (JAMA Surg) found that the indication for stent placement (myocardial infarction versus acute coronary syndrome or no acute coronary syndrome) was associated with a marked increase in odds ratio for MACE, especially with surgery during the first 3 months after stent implant. Holcomb et al (Ann Surg) also compared the risk of MACE in more than 9000 patients undergoing noncardiac surgery within 24 months of stent placement with twice as many patients, matched for surgical and cardiac risk factors, who had not received coronary stents, from the VA Surgical Quality Improvement Program (VASQUIP) data. The rate of MACE, myocardial infarction, and revascularization was much higher in the stent patients, but mortality was not higher.

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Bloom MB, Zaw AA, Hoang DM, et al. Body mass index strongly impacts the diagnosis and incidence of heparin-induced thrombocytopenia in the surgical intensive care unit. J Trauma Acute Care Surg. 2016;80:398–403.

In this single-center prospective observational study, Bloom et al assessed the association of obesity (body mass index) on the incidence of heparin-induced thrombocytopenia (HIT) in 304 patients in their general and cardiac surgery intensive care units (ICUs), with the clinical suspicion of HIT. They observed that the incidence of HIT was strongly associated with increasing body mass index (BMI). Compared with patients with a normal BMI, the odds ratio for HIT with a BMI of 30 to <40 was 2.9 (95% CI, 1.2–7.5), and for a BMI of ≥40, it was 7.0 (95% CI 1.6–28.2). The mechanism for this observed association requires further investigation. In the meantime, the authors suggested that patients’ obesity (thickness) should be a fifth “T” to help to predict the diagnosis of HIT.

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Neufeld KJ, Yue J, Robinson TN, et al. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis. J Am Geriatr Soc. 2016;64:705–714.

Carrasco G, Baeza N, Cabré L, et al. Dexmedetomidine for the treatment of hyperactive delirium refractory to haloperidol in nonintubated ICU patients: a nonrandomized controlled trial. Crit Care Med. 2016;44:1295–1306.

In their systematic review and meta-analysis of 19 studies, Neufeld et al found that the use of antipsychotics (compared with placebo or no treatment) was not associated with a significant decreased incidence of delirium, nor with a decrease in delirium severity, duration, intensive care unit (ICU) or hospital length of stay, or mortality. However, the authors opined that more rigorous studies are needed. In an observational trial, Carrasco et al treated 132 nonintubated ICU patients with hyperactive delirium with a haloperidol titration. A total of 35% were nonresponders. Dexmedetomidine was then added to these nonresponders, and 93% achieved satisfactory sedation; the use of dexmedetomidine was also associated with a shorter ICU stay and less excessive sedation. Despite the limitations of this nonblinded observational trial, the accompanying editorial by Teegarden and Prough (Crit Care Med. 2016;44:1426–1428) concluded that this study adds to the evidence supporting the use of dexmedetomidine in the treatment of delirium. (See also Reade MC et al, JAMA. 2016;315:1460–1468, as reviewed in “Surveying the Literature” in the July 2016 issue of Anesthesia & Analgesia.)

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Plews-Ogan M, May N, Owens J, et al. Wisdom in medicine: what helps physicians after a medical error? Acad Med. 2016;91:233–241.

“To err is human” is well accepted, and many physicians have committed or will commit a serious medical error. The physician is the second victim of such errors, which may lead to clinician depression, leaving his or her practice, or even suicide. On the basis of semistructured interviews and quantitative measures, these investigators studied 61 physicians who had made serious medical errors. The investigators identified 8 themes that helped these physicians to achieve positive post-traumatic growth and wisdom after their experiences. The authors made recommendations for peer support programs and for institutions to promote positive response after a medical error. All anesthesiologists can likely benefit from studying this article.

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  1. Frankel HL, Kirkpatrick AW, Elbarbary M, et al. Guidelines for the appropriate use of bedside general and cardiac ultrasonography in the evaluation of critically ill patients—part I: general ultrasonography. Crit Care Med. 2015;43:2479–2502.
  2. Levitov A, Frankel HL, Blaivas M, et al. Guidelines for the appropriate use of bedside general and cardiac ultrasonography in the evaluation of critically ill patients—part II: cardiac ultrasonography. Crit Care Med. 2016;44:1206–1227.
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© 2016 International Anesthesia Research Society