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Article 1
Intraoperative hypotensive resuscitation for patients undergoing laparotomy or thoracotomy for trauma: early termination of a randomized prospective clinical trial. Carrick MM, Morrison CA, Tapia NM, Leonard J, Suliburk JW, Norman MA, Welsh FJ, Scott BG, Liscum KR, Raty SR, Wall MJ Jr, Mattox KL. J Trauma Acute Care Surg. 2016 Jun;80(6):886-96.
This manuscript supplements the landmark 1994 New England Journal of Medicine paper by Bickell and colleagues1. It attempts to prove that allowing patients dying of hemorrhagic shock to remain hypotensive during operative control of blood loss improves survival relative to increasing the blood pressure during times of unchecked hemorrhage. The results of these data show no statistical difference in mortality between patients undergoing emergent laparotomy or thoracotomy who are resuscitated to a mean arterial blood pressure (MAP) greater than 50 mmHg and those resuscitated to a MAP greater than 65 mmHg (21.4% vs 26.3%, p= 0.48). This trail was terminated after enrolling 180 patients (short of the target 271) because of a futility in reaching the primary endpoint (30 day mortality). Despite the negative findings of the study, the value of this manuscript to the surgical literature cannot be understated, as there is much to learn from the study design, execution and collected data.
First, this paper underscores the importance of considering language when describing various resuscitation strategies. In many cases, “volume restrictive” strategies do not equate with “hypotensive resuscitation” strategies. In this paper, the average MAP of the hypotensive patients was 65.5. The average MAP of the control patients was 69.1. Not by any fault of the investigators, rather because of the remarkable ability of human physiology (even in the face of overwhelming hemorrhagic shock) to maintain near normal MAP. In that regard, pairing this study with Bickell’s 1994 paper will prove an invaluable tool in the education of anyone interested in resuscitation. Additionally, this project represents a herculean effort to design and execute high quality medical research in trauma. However, as a single institute, with a narrow population sample (young people dying from hemorrhagic shock), it took over 7 years to collect enough data draw meaningful conclusions. As the authors correctly acknowledge, temporal confounding certainly influenced their results. This should serve as a warning to other investigators interesting in similar projects. It highlights the importance exact pilot data for reliable sample and effect size calculations and it underscores the importance of collaboration in the timely execution of medical research.
- Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. Bickell WH, Wall MJ, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL. N Engl J Med. 1994 Oct 27;331(17):1105-9.
Article 2
High value care in the surgical intensive care unit: effect on ancillary resources. Ko A, Murry JS, Hoang DM, Harada MY, Aquino L, Coffey C, Sax HC, Alban RF. J Surg Res. 2016 May 15;202(2):455-60.
This paper compares frequency of lab test and x-ray utilization before and after the implementation of a Lean Sigma Six based high value care process in a single, 24 bed academic surgical intensive care unit. The intervention included a daily checklist for rounding physicians, clinical education, visual cues and the standardization of continuous capnography on ventilated patients. Outcomes included number of lab and x-ray tests ordered, estimated direct costs, clinical patient and ICU metrics (such as lengths of stay and case mix index), and mortality. Authors do not supply costs associated with the implementation of continues capnography. These authors do an outstanding job demonstrating the decreased frequency of lab and x-ray utilization after roll out of a high value care process (such as a 54.1% reduction in use of arterial blood gas analysis). Similarly the estimated cost reduction is notable (projected savings of $710,000 per year). Coincidentally, the authors demonstrate that there was no change in mortality that occurred during the same time period.
The reader should be cautioned, however, in that the only patient centered clinical outcome measured was mortality. While it is comforting that absolute mortality decreased during the study period (7.1% to 5.1%), assuming that the high value care process did not cause any harm to the patients is dangerous. The reader is reminded that outcome equality and non-inferiority are not the same, and the ability to detect a statistical difference between anything occurring with frequencies of 7% and 5% requires huge sample sizes. Furthermore the presented data does not inform the reader to any other clinically meaningful ICU outcomes such as infection rates, antibiotic days, unplanned extubation rates, blood transfusion occurrences, etc. None the less, this study is an important contribution and building block for future value based care initiatives.
Article 3
Efficacy and safety of glutamine-supplemental parenteral nutrition in surgical ICU patients. Ziegler TR, May AK, Hebbar G, Easley KA, Griffith DP, Dave N, Collier BR, Cotsonis GA, Hao L, Leong T, Manatunga AK, Rosenberg ES, Jones DP, Martin GS, Jensen GL, Sax HC, Kudsk KA, Galloway JR, Blumberg HM, Evans ME, Wischmeyer PE. Ann Surg. 2016 Apr;263(4):646-55.
This is a phase III, double blind, randomized controlled trial of glutamine supplemented versus standard parenteral nutrition (PN) in 150 gastrointestinal, vascular or cardiac surgery patients in 5 major independent medical center intensive care units. This study adds to a growing body of mixed ICU literature suggesting decreased hospital acquired infections and increased survival after supplementation of parenteral nutrition with glutamine. And it specifically addresses the safety of glutamine supplementation on the heels of the REDOXS RCT, which suggested increased mortality among patients receiving high dose glutamine supplementation.1 In the current study, there was no differences in hospital infections between glutamine supplemented and standard PN (28% vs. 25%, p=0.70). Additionally, there was no difference in mortality between the groups (14.7% vs. 17.3%, p=0.66).
There are some important caveats that are worth consideration regarding the generalizability of the study. First, the study design excluded many common surgical ICU patients, specifically, patients with septic shock, trauma, burns, malignancy, cirrhosis, or chronic renal failure (including new serum creatinine > 2.5 mg/dL). This strengthens the study in regards to demonstrating the safety of glutamine supplementation (there were no effects of treatment on serum renal or hepatic markers of injury), but certainly limits it’s applicability to many SICU patients. The authors offer keen insight regarding the evolution of many of the surgical procedures towards less catabolic surgeries (laparoscopy and endovascular) over the duration of glutamine studies.
- A randomized trial of glutamine and antioxidants in critically ill patients. Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. N Engl J Med. 2013;368:1489-1497.
Article 4
Age, PaO2/FIO2, and Plateau Pressure Score: A Proposal for a Simple Outcome Score in Patients With the Acute Respiratory Distress Syndrome. Villar J, Ambrós A, Soler JA, Martínez D, Ferrando C, Solano R, Mosteiro F, Blanco J, Martín-Rodríguez C, Fernández MM, López J, Díaz-Domínguez FJ, Andaluz-Ojeda D, Merayo E, Pérez-Méndez L, Fernández RL, Kacmarek RM; Stratification and Outcome of Acute Respiratory Distress Syndrome (STANDARDS) Network. Crit Care Med. 2016 Jul;44(7):1361-9.
These authors propose a 3 variable (1–9-point total) scoring system to quantify the risk of mortality associated with the acute respiratory distress syndrome (ARDS). Essentially, they used iterative regression analyses derived from a sample of 300 consecutive adult ARDS patients 24 hours after admission to a network ICU between September 2008 and January 2010. Based on these regressions, they constructed the 9 point risk assessment tool which considers patient age, P/F ratio and plateau pressure. This model was validated in a spate cohort of 300 consecutive ARDS patients. The AUC of the test (predicting mortality) in the validation cohort was 0.800, and it outperformed the APACHE II score.
The value of this study lies not in the score itself, but the proposal and execution of the concept. The model likely offers a reasonable tool for prognostication. It will probably be refined and made more precise in years to come. However, it is an outstanding starting point. This is particularly true for intensivists at the bedside who must explain the natural history of the disease and weight the risks and benefits of treatment options (abandoning traditional ventilation strategies or progressing to ECMO) as the pathophysiology changes.
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