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Article 1
Direct to operating room trauma resuscitation decreases mortality among severely injured children. Wieck MM, Cunningham AJ, Behrens B, Ohm ET, Maxwell BG, Hamilton NA, Adams MC, Cole FJ Jr, Jafri MA. J Trauma Acute Care Surg. 2018 Oct;85(4):659-664.
Some adult trauma centers have successfully implemented direct to operating room (DOR) resuscitation. This involves bypassing the trauma bay and taking the patient directly to the OR for evaluation and any necessary interventions. This process has been shown to decrease time to operative intervention and improve survival in adult patients but has not been studied in pediatric patients. Wieck et al. aimed to evaluate their urban ACS Level 1 Pediatric Trauma Center experience with DOR resuscitation. This was a retrospective review of their prospectively-maintained database over eight years (2009-2016). 82 patients were included in the analysis. 76% were admitted from the field with 24% transferring from a referring hospital. The following criteria were used for DOR admission (with proportion of study patients with each criteria): chest injury (32%); rigid, distended abdomen (1%); evisceration of abdominal contents (4%); penetrating injury, including impaled object, in neck, chest, abdomen, or pelvis (62%); traumatic amputations (6%); age-specific hypotension (11%); significant blood loss on scene or in route (7%); cardiopulmonary arrest due to trauma (11%); physician discretion (15%).
82% of DOR patients required emergent procedural intervention. Though the most commonly performed procedure was wound exploration or repair, 54% required major procedures (laparotomy, thoracotomy, craniotomy, neck exploration or vascular repair). Overall survival of these patients was 84%. None of the above criteria was an individually significant predictor of the need for emergent intervention. Observed mortality was compared to expected mortality using TRISS (Trauma Injury Severity Score) methodology. Overall, DOR patients had a trend toward lower mortality (16% observed vs 21% predicted) but this was only significant in penetrating trauma (16% observed vs 26% predicted). Overall hospital costs for DOR patients compared to non-DOR patients were similar.
A protocol for DOR resuscitation of severely injured pediatric patients shows a trend to reduction in overall mortality in the appropriate patients. This mortality benefit is statistically significant in penetrating trauma. Trauma centers that have the available resources and structural footprint to do so, should consider DOR resuscitation for select pediatric patients.
Article 2
Individual and neighborhood characteristics of children seeking emergency department care for firearm injuries within the PECARN network. Carter PM, Cook LJ, Macy ML, Zonfrillo MR, Stanley RM, Chamberlain JM, Fein JA, Alpern ER, Cunningham RM. Acad Emerg Med. 2017 Jul;24(7):803-813.
Firearm violence was the second leading cause of death among United States children in 2013. A prominent focus in the literature has been on fatal firearm injuries in children, whereas there is a deficit of information regarding children sustaining nonfatal firearm injuries. This paper by Carter et al. aimed to evaluate the characteristics of children with nonfatal firearm injuries as well as describe the individual and neighborhood risk factors for these injuries. The study was a secondary analysis of data from the PECARN (Pediatric Emergency Care Applied Research Network) core data project. The study evaluated data from 16 hospitals over five years (2004-2008). There was a total of 1,758 ED visits included in the study. The prevalence of firearm injuries overall increased with increasing age. Additionally, the proportion of assault injury (compared to self-inflicted and unintentional injuries) increased with increasing age; however, it must be noted that unintentional firearm injury is a significant problem in the younger age groups (<10 years old). A multivariate analysis compared firearm-related injury visits to non-firearm-related visits to the ED and this demonstrated the following risk factors among children for nonfatal firearm injuries: male sex, minority race/ethnicity, older aged youth and higher neighborhood socioeconomic disadvantage.
Male sex, minority status, adolescence and socioeconomic disadvantage are independent risk factors among children for nonfatal firearm injury. These risk factors can help guide further efforts in prevention of firearm injuries whether they be accidental or assault. An interesting side note seen in the study described that almost 20% of children suffering a firearm injury had been seen in the same ED within the prior 12 months, potentially allowing an opportunity for preventative counseling.
Article 3
Twenty years of pediatric gunshot wounds in our community: Have we made a difference? Bayouth L, Lukens-Bull K, Gurien L, Tepas III JJ, Crandall M. J Pediatr Surg. 2019 Jan;54(1):160-164.
Over the last two decades firearm violence is responsible for the death of more than 35,000 children. As aforementioned firearm injury has become the second leading cause of pediatric death. Bayouth et al. aimed to evaluate the pediatric firearm injuries seen over the last 20 years (1996-2016) at their Level 1 Trauma Center in Jacksonville, FL (located in the most violent urban county of the state). This was a retrospective review of the center’s trauma registry that included all patients age 0-18 years who suffered a gunshot wound (GSW). 898 patients were identified. 81.5% of GSWs were assaultive. There was an overall mortality rate of 10%. There was a significant variation in annual incidence of GSWs but no overall longitudinal trend during the study period. Geographic information system (GIS) mapping demonstrated significant geographic clustering of GSWs with one particular zip code having the highest overall and annual incidence of GSWs. The highest rates of GSWs occurred in zip codes that were the most socioeconomically and resource impoverished with no change over time despite multiple efforts including increased police presence, violence intervention programs and aggressive seizure of illegal firearms.
Pediatric firearm violence is most prevalent in socioeconomically deprived areas in this urban center. Though this may or may not be reliably generalized to other urban areas, an assumption could be made that this is common based on other previous studies including that by Carter et al. above. Most importantly, the addition of violence intervention programs and increased policing have not been able to combat the socioeconomic factors that appear to be driving the prevalent firearm violence in the high-hazard areas of the city, suggesting that other, potentially higher-level, interventions are needed to counteract the socioeconomic forces driving violence in these areas.
Article 4
Effect of Haloperidol on Survival Among Critically Ill Adults with a High Risk of Delirium:
The REDUCE Randomized Clinical Trial. Van den Boogaard M, Slooter AJC, Brüggemann RJM, Schoonhoven L, Beishuizen A, Vermeijden JW, Pretorius D; de Koning J, Simons KS, Dennesen PJW, Van der Voort PHJ, Houterman S, van der Hoeven JG, Pickkers P, REDUCE Study Investigators, van der Woude, Besselink A, Hofstra LS, Spronk PE, van den Bergh W, Donker DW, Fuchs M, Karakus A, Koeman M, van Duijnhoven M, Hannink G. JAMA. 2018 Feb 20; 319(7): 680–690.
The REDUCE (Prophylactic Haloperidol Use for Delirium in ICU Patients at High Risk for Delirium) trial was a 3-year prospective, double-blind, placebo controlled, randomized clinical trial (RCT) involving 21 sites in the Netherlands. The RCT randomized critically ill adults to one of 3 treatment arms: 1) 1 mg haloperidol three times a day, 2) 2 mg haloperidol three times a day or 3) Normal saline placebo three times a day. All adults over 18 years-old in the ICU who were delirium-free and expected to have an ICU stay over 2 days were included. The main exclusion criteria included increased risk for baseline cognitive dysfunction (delirium, Parkinson’s disease, dementia, alcoholic abuse, acute neurologic condition, and psychiatric disease), increased risk for haloperidol side effects (known allergy, history of ventricular tachycardia, and QTc>500ms), pregnant or breastfeeding and expected death within 2 days. The primary outcome was 28-day mortality. Prophylactic haloperidol did not reduce 28-day mortality in ICU patients (difference 0 days, HR:1.003, 95% CI 0.78-1.30.)
This RCT was conducted in the Netherlands from July 2013 to December 2016 at 21 clinical sites including university, teaching and nonteaching hospitals during which time 15,882 patients were screened ultimately randomizing 1796 critically ill adults into the three arms with 353 in the 1 mg arm, 734 in the 2mg arm and 709 into the placebo arm. Due to the adaptive design of the trial the 1 mg arm was abandoned due to a futility analysis after enrollment of 350 subjects. Ultimately the primary analysis included 350 in the 1 mg arm, 732 in the 2 mg arm, and 707 in the placebo arm. Regarding the primary outcome there was no statistically significant difference between the 2 mg and placebo groups with both the 2 mg group and the placebo groups demonstrating a median survival in 28 days of 28. For all secondary outcomes including 90-day survival, delirium incidence and delirium and coma-free days no statistically significant differences were noted between the groups. No significant differences were found in adverse events, including QT prolongation or extrapyramidal symptoms, between the treatment and placebo groups. Subgroup analyses were preformed per admission diagnosis, severity of illness and delirium prediction scores and again no differences were found between intervention and placebo. The REDUCE trial shows there is no role for low-dose haloperidol in the prevention of ICU delirium, although there was no harm associated with haloperidol prophylaxis there also is no meaningful clinically relevant benefit. What will a treatment RCT for delirium using higher haloperidol doses, like the MIND-USA Study show ? Stay tuned…
Additional References for Article 4:
Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, Pun BT, Thompson JL, Shintani AK, Meltzer HY, Bernard GR, Dittus RS, Ely EW; MIND Trial Investigators. Crit Care Med. 2010 Feb;38(2):428-37.
Article 5
Balanced Crystalloids versus Saline in Critically Ill Adults. Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. N Engl J Med. 2018 Mar 1;378(9):829-839.
The SMART (Isotonic Solutions and Major Adverse Renal Events Trial) study was a two-year, five intensive care unit (ICU), single center study pragmatic, unblinded, cluster-randomized, multiple-crossover trial. Under waiver of informed consent and according to randomization of ICU, this trial assigned critically ill adults to 1) saline (0.9% sodium chloride) or 2) balanced crystalloid (lactated Ringer’s solution or Plasma-Lyte A) for intravenous fluid administration. The primary outcome was a major adverse kidney event (i.e., composite renal outcome including death, new renal-replacement therapy, or persistent renal dysfunction) within 30 days or hospital discharge, whichever occurred first. The use of balanced crystalloids for intravenous fluid administration in ICU patients resulted in a lower rate of the composite outcome (14.3% versus 15.4%; marginal OR=0.91 [95%CI: 0.84-0.99]; conditional OR=0.90 [95%CI:0.82-0.99, P=0.04]).
This trial was conducted at Vanderbilt from June 2015 to April 2017 enrolling 15,802 adults across Medical, Neurologic, Cardiac, Trauma, and Surgical ICUs. More than one third of patients were receiving mechanical ventilation and one quarter were receiving vasopressors at enrollment. The median volume of balanced crystalloids administered was 1000 mL (IQR: 0-3210), and the median volume of saline administered was 1020 mL (IQR: 0-3500). For the primary outcome, the results were similar as above in six prespecified sensitivity analyses: 1) including only those who received >=500 mL of crystalloid in the 72 hours post-enrollment, 2) excluding admissions in the week preceding a crossover in the fluid assigned to the ICU, 3) excluding those transferred between ICUs or remained in the ICU through a crossover, 4) including only the first ICU admission, 5) addressing missing values for baseline creatinine levels, and 6) using alternative modeling approaches. The results suggest that the use of balanced crystalloids (rather than saline) might prevent 1 in 94 ICU patients from needing new renal-replacement therapy, persistent renal dysfunction, or death, which is substantial considering 5 million patients are admitted to ICUs per year.
Additional References for Article 5:
Isotonic Solutions and Major Adverse Renal Events Trial (SMART) Investigators; Pragmatic Critical Care Research Group. Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial. Semler MW, Self WH, Wang L, Byrne DW, Wanderer JP, Ehrenfeld JM, Stollings JL, Kumar AB, Hernandez A, Guillamondegui OD, May AK, Siew ED, Shaw AD, Bernard GR, Rice T. Trials. 2017 Mar 16;18(1):129.
Article 6
Timing of Renal-Replacement Therapy in Patients with Acute Kidney Injury and Sepsis. Barbar SD, Clere-Jehl R, Bourredjem A, Hernu R, Montini F, Bruyère R, Lebert C, Bohé J, Badie J, Eraldi JP, Rigaud JP, Levy B, et al., for the IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network. N Engl J Med. 2018; 379:1431-1442.
The IDEAL-ICUs (Initiation of Dialysis Early Versus Delayed in the Intensive Care Unit) trial was a roughly 4-year prospective randomized controlled open-label clinical trial (RCT). The RCT assigned adult patients with early septic shock (with 48h of vasopressors) and acute kidney injury (failure stage of the RIFLE classification) to either A) early-strategy (within 12h of documented renal injury) or B) delayed-strategy (after 48h without renal recovery) . The main exclusion criterion was pre-randomization requirement of emergency renal-replacement therapy. The primary outcome was 90 days mortality. The early initiation of renal-replacement therapy did not result in lower mortality at 90 days than the delayed strategy (58% vs 54%, P=0.38).
This French RCT was conducted from July 2012 to October 2016 across 29 ICUs ultimately randomizing 488 patients (246 early-strategy group, 242 late-strategy group). There was no difference in fluid balance among groups 24h pre-randomization, 48h post-enrollment, or at 7 days. In the early-strategy group, 97% (239 of 246) received renal-replacement therapy in a median time of 7.6h (IQR: 4.4-11.5). In the delayed-strategy group, 62% (149 of 242) received renal-replacement therapy in a median time of 51.5h (IQR: 34.6-59.5) while 29% (70) demonstrated spontaneous renal recovery. In the early-strategy group 58% died (138 of 239) and in the delayed-strategy group 54% died (128 of 238), P=0.38. As a pre-specified secondary outcome, the delayed strategy resulted in 16 days free of renal-replacement therapy (IQR: 2-28) while the early strategy resulted in 12 days free of renal-replacement therapy (IQR: 1-25), P=0.006. However, the rate of dependence on renal-replacement therapy among survivors at 28 days did not differ between the groups. Despite the limitation of the short-time period for the delayed strategy, the IDEAL-ICU study shows that initiating renal-replacement therapy within 12h of acute kidney injury with failure versus 48h had no difference on mortality, and early renal replacement could unnecessarily expose those with potential spontaneous renal recovery to dialysis.
Additional References for Article 6:
Impact on mortality of the timing of renal replacement therapy in patients with severe acute kidney injury in septic shock: the IDEAL-ICU study (initiation of dialysis early versus delayed in the intensive care unit): study protocol for a randomized controlled trial. Barbar SD, Binquet C, Monchi M, Bruyère R, Quenot JP. Trials. 2014 Jul 7;15:270.
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