García et al. World Journal of World Journal of Emergency Surgery (2023) 18:4 https://doi.org/10.1186/s13017-023-00475-x Emergency Surgery RESEARCH Open Access Hypertonic saline infusion does not improve the chance of primary fascial closure after damage control laparotomy: a randomized controlled trial Alberto F. García1,2,3,4*, Ramiro Manzano‑Nunez5,6,7, Diana Cristina Carrillo3, Julian Chica‑Yanten3, María Paula Naranjo3,11, Álvaro I. Sánchez1,3, Jorge Humberto Mejía2, Gustavo Adolfo Ospina‑Tascón2,9, Carlos A. Ordoñez1,2,4, Juan Gabriel Bayona10 and Juan Carlos Puyana8 Abstract Background Previous observational studies showed higher rates of abdominal wall closure with the use of hyper‑ tonic saline in trauma patients with abdominal injuries. However, no randomized controlled trials have been per‑ formed on this matter. This double-blind randomized clinical trial assessed the effect of 3% hypertonic saline (HS) solution on primary fascial closure and the timing of abdominal wall closure among patients who underwent damage control laparotomy for bleeding control. Methods Double-blind randomized clinical trial. Patients with abdominal injuries requiring damage control lapa‑ rotomy (DCL) were randomly allocated to receive a 72-h infusion (rate: 50 mL/h) of 3% HS or 0.9 N isotonic saline (NS) after the index DCL. The primary endpoint was the proportion of patients with abdominal wall closure in the first seven days after the index DCL. Results The study was suspended in the first interim analysis because of futility. A total of 52 patients were included. Of these, 27 and 25 were randomly allocated to NS and HS, respectively. There were no significant differences in the rates of abdominal wall closure between groups (HS: 19 [79.2%] vs. NS: 17 [70.8%]; p = 0.71). In contrast, significantly higher hypernatremia rates were observed in the HS group (HS: 11 [44%] vs. NS: 1 [3.7%]; p < 0.001). Conclusion This double-blind randomized clinical trial showed no benefit of HS solution in primary fascial closure rates. Patients randomized to HS had higher sodium concentrations after the first day and were more likely to present hypernatremia. We do not recommend using HS in patients undergoing damage control laparotomy. Trial registration The trial protocol was registered in clinicaltrials.gov (identifier: NCT02542241). Keywords Damage control surgery, Abdominal injuries, Hypertonic saline, Trauma and injuries *Correspondence: Alberto F. García alberto.garcia@fvl.org.co; alberto.garcia@correounivalle.edu.co Full list of author information is available at the end of the article © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. García et al. World Journal of Emergency Surgery (2023) 18:4 Page 2 of 10 Introduction all patients or another surrogate decision-maker. Con- Since patients with abdominal trauma often present sent by an independent physician and deferred consent severe injuries and impaired physiology, they tend to was used as a surrogate to subject consent when appro- require damage-control abdominal surgery followed by priate. In these cases, the trial team performed the ran- damage-control resuscitation [1, 2]. Trauma surgeons domization following pre-specified trial protocol criteria treating these patients prioritize bleeding and contami- and then requested for the patient’s or representative’s nation control and leave the abdomen open during sur- (proxy) informed consent in a later phase. gery [3]. Then, patients are transferred to the ICU for An independent committee and the staff from the FVL appropriate monitoring and hemostatic resuscitation. clinical research center regularly monitored the trial to One of the objectives of the damage-control approach check for protocol compliance and data transparency. is to prioritize physiology stabilization before defini- tive injury repair and abdominal wall closure. However, Patients trauma surgeons often face the trade-off between leaving Adult patients with traumatic injuries were eligible for the abdominal wall open beyond the necessary time and the study if they were to undergo damage control abdom- the complications that can arise from an open abdomen. inal surgery in the index laparotomy. Specific inclusion Therefore, interventions to enhance resuscitation while criteria were: 1. informed consent obtained before any simultaneously reducing the time in which an open abdo- trial-related activities, 2. age above or equal to 18 years at men is required, improving the chance of achieving early the time of inclusion, and 3. patients with blunt or pene- abdominal wall closure, are needed. trating trauma and requiring DCL for abdominal injuries. A potential intervention to reduce the volume of intra- The decision to perform an emergent laparotomy was venous fluids infused without putting resuscitation in taken by the attending trauma surgeon at the emergency peril is hypertonic saline (HS) infusion [4, 5]. Prior obser- department in patients with signs of exsanguination/ vational studies have shown improved outcomes [6–8], hemodynamic instability, acute abdomen or eviscera- including higher rates of abdominal wall closure with tion. When in the operating room, patients underwent a reduced times to it with the use of HS during the resusci- DCL (involving surgical control of bleeding and contami- tation of injured patients with abdominal trauma requir- nation plus packing with laparotomy pads plus leaving ing damage control surgery with an open abdomen. the abdominal wall open) if there was evidence of hypo- However, these studies are observational, retrospective, thermia, metabolic acidosis or hyperlactatemia (reflect- and prone to bias. Thus, comprising the validity and clin- ing physiological exhaustion), hemoperitoneum and/or ical applicability of their results. Here, we present a dou- destructive intra-abdominal organ injuries. A detailed ble-blind, randomized clinical trial to assess the effect of description on how we approach and provide surgical 3% hypertonic saline solution on primary fascial closure treatment to patients with abdominal injuries requiring and the timing of abdominal wall closure among patients damage-control surgery at our institution is described who underwent damage control laparotomy (DCL) for elsewhere [9, 10]. bleeding control. Exclusion criteria Methods Patients were excluded if the time between the occur- Setting, study design, and oversight rence of his/her traumatic injuries and the randomization This double-blind, randomized, placebo-controlled trial was longer than four hours, had a severe traumatic brain was conducted at Fundación Valle del Lili (FVL) Univer- injury, and had a high probability of death in the first sity hospital between November 2015 and August 2018. 48 h. Although the treating surgeon subjectively deter- The FVL is a fourth-level university hospital equivalent mined this, the decision was based on what is known to a US-level I trauma center, and it has 523 beds. Of about the epidemiology of deaths after trauma [11–13]. these, 205 are ICU beds and 10 are reserved for trauma Therefore, patients with a high probability of death dur- patients. The FVL trauma center admits approximately ing the first 48 h were those with destructive lesions asso- 700 moderate-to-severe trauma patients per year, serving ciated with major exanguination leading to refractory as one of the largest trauma referral centers in the south- shock. For example, patients with abdominal injuries and west region of Colombia. concomitant/coexistent high grade ≥ 4 solid organ inju- The trial protocol was registered in clinicaltrials.gov ries, severe pulmonary injuries causing massive hemo- (identifier: NCT02542241). The protocol was designed thorax, heart injuries, or single/multiple injuries to major by the Trial Steering Committee and was reviewed and named axial torso vessels. approved by the FVL ethical and biomedical research Patients were also excluded if the indications for per- committee. Written informed consent was obtained from forming a DCL were different from the initial trauma García et al. World Journal of Emergency Surgery (2023) 18:4 Page 3 of 10 (i.e., DCL in the context of post-traumatic intrabdominal definitive abdominal wall closure when: all the injuries infections, patients in whom the abdomen was closed at are correctly managed, the patient physiology is stabi- the index surgery but required an emergent relaparotomy lized, and there is no evidence of abdominal contamina- for postoperative bleeding or control of contamination). tion focuses/absence of intra-abdominal infections. Also, Pregnant women were also excluded. definitive closure is performed when the abdominal cav- ity can be closed without tension. Other factors that the Study protocol surgeon considers to perform definitive closure are the Patients in both study groups received trauma care in the fluid balance, the intestinal edema found at surgery, and emergency department and the operating group follow- the change in the airway pressure or the tidal volume ing current clinical practice guidelines and institutional during the procedure. protocols. After the decision to perform a DCL, patients underwent randomization in a double-blind manner. Study end points and definitions Randomization was performed in permuted blocks of The primary endpoint of the trial was the proportion of dom Allocation Software® [14]. The assignment was four and six by an independent statistician using Ran- patients with abdominal wall closure in the first seven days after the index surgery. concealed until consent was given. Then, the investigator Secondary endpoints were: 28-day mortality, the fluid confirmed the inclusion in an internet-based platform, balance during the first 72 h, the proportion of patients which revealed the allocation after confirming the con- requiring reoperation for intra-abdominal hypertension, sent and the inclusion criteria. Regularly, randomization the proportion of patients with abdominal compart- happened immediately after the index surgery when pre- ment syndrome (defined as sustained intra-abdominal paring for the transfer to the ICU or in the first minutes pressure > 20 mm Hg and a new organic dysfunction), in the ICU. the proportion of patients with organic dysfunction, According to their allocation, the patients received a defined as a Sequential Organ Failure Assessment (SOFA 72-h infusion (rate: 50 mL/h) of 3 N hypertonic saline score) > 2 [16], the proportion of patients with ARDS or 0.9 N isotonic saline after the index damage control [17], and the proportion of patients with hypernatremia. laparotomy. The infusion was administered in the inten- sive care unit. The presentation of the study solutions Statistical analysis was similar. Neither the treating group nor the patients The trial was designed on the assumption of the superior- nor the investigators could discern their composition. ity principle to have 80% power with a p < 0.05 to detect The treating team made decisions regarding other flu- a 60-to-75% difference in the probability of closing the ids, blood components, vasopressors, inotropic support, abdomen on the seventh day after the index laparotomy or monitoring according to the usual practice. The study with the therapy with hypertonic saline. With the addi- infusion was considered at all times when planning and tion of 20% for losses, we calculated 200 patients needed executing fluid resuscitation. Double-blind was achieved in each study group. by the use of similar appearing saline bags in the two The trial team had full access to the data and was groups. responsible for the analysis. All analyses were performed Decisions regarding the timing of the reoperations in a blinded manner so that investigators could not know and the abdominal closure were made by the surgical if subjects were assigned to the control or treatment Statistical analyses were performed on Stata 15.1® team according to the need for reconstruction of spe- group. cific lesions, the occurrence of complications, and the fluid balance. In each patient, the surgeons worked to (College Station, Tx). Categorical variables are presented reconstruct the lesions and close the abdomen as early as as frequencies and percentages. The normality of con- possible. tinuous variables was examined by the Shapiro–Wilk The protocol for organ injury management and abdom- test. Afterward, they are presented as mean and standard inal wall closure has been previously published [9, 10, deviation or median and interquartile rank. 15]. In brief, delayed abdominal closure was considered Categorical variables were compared with C ­ hi2 or Fish- a bridge to achieve three main goals: 1. compartment er’s Exact Test, as indicated. Continuous with Student’s T syndrome prevention, 2. definitive control of bleed- test or Wilcoxon–Mann–Whitney according to normal- ing and contamination, and 3. definitive wound heal- ity. Time-to-event variables were presented as Kaplan– ing. Therefore, the first reoperation was performed as Meier curves and compared with the Logrank test. early as possible after correcting the patient’s physi- Interim analyses were planned at enrollment of 50, ological derangement (control of acidosis, hypothermia, 100, 200, and 300 patients, with predefined termina- and coagulopathy). It is our surgical practice to perform tion criteria for futility or effectivity [18]. We chose the García et al. World Journal of Emergency Surgery (2023) 18:4 Page 4 of 10 Haybittle-Peto criteria [19, 20] for stopping for effectiv- mm Hg, 23 (19–29.5), and 14 (12.5–15), respectively. ity and the analysis of conditional power for stopping for (Table 1). futility [21, 22]. The anatomic severity of injuries, measured by the ISS [23] and ATI [24] scores, was classified as severe in more than 50% of the cases and critical in about one-fourth Results (Table 1). The most frequently compromised structure The study was suspended in the first interim analysis was the major vessels in the abdomen (75%), followed by because of futility. Of the 61 screened patients, nine were the hollow viscus (63.5%) and the liver (48%) (Table 1). excluded. The most frequent cause was the notification to In 88.5% of the cases, an additional damage control the investigation group after the 4-h limit. Figure 1 shows procedure was required for the repair of an injury out- the CONSORT flow diagram for the present randomized side the abdomen. The abdominal cavity was transiently trial. closed with a negative pressure-assisted system in all A total of 52 patients were included, and 44 (84.6%) patients. A commercial device was used in 90.4% of the were male. The trauma mechanism was penetrating in patients (Table 1). 41 cases (78.9%). The physiologic derangement was mod- Twenty-seven patients were randomly assigned to erate at admission, with a median interquartile range normal saline (NS) and 25 to 3 N hypertonic saline (HS) (IQR) of RTS of 7.11 (6.08–7.84) (Table 1). The median (Fig. 1). The comparison between the groups did not interquartile range (IQR) of systolic blood pressure, res- show differences in the demographic information, the piratory rate, and Glasgow coma scale were 90 (20–122) trauma mechanism or severity, the injured organs, the Fig. 1 Consort flow diagram García et al. World Journal of Emergency Surgery (2023) 18:4 Page 5 of 10 Table 1 Hypertonic saline after a damage control laparotomy. Randomized controlled clinical trial. Baseline information Variable Total NS HS Patients, n (%) 52 27 25 Age, mean (SD) 35.1(± 14.1) 32.9 (± 13.9) 37.5 (± 14.1) Male, n (%) 44 (84.6%) 22 (81.5%) 22 (88.0%) Trauma mechanism Penetrating, n (%) 41 (78.9%) 24 (88.9%) 17 (68.0%) Blunt, n (%) 11 (21.1%) 3 (11.1%) 8 (32.0%) Systolic BP, mm Hg, median (IQR) 90 (60–122) 80 (60–129) 91 (60–112) Respiratory rate, breaths/min, median (IQR) 23 (19–29.5) 22 (19–30) 24 (19–28) Glasgow Coma Score, median (IQR) 14 (12.5–15) 15 (10–15) 14 (13–15) RTSt, median (IQR) 11 (9 − 12) 11 (9 −12) 11 (10 −12) RTSs, median (IQR) 7.11 (6.08–7.84) 7.11 (5.78–7.84) 7.11 (6.38–7.84) AIS thorax, median (IQR) 0 (0 -3) 0 (0–3) 0 (0–3) AIS abdomen, median (IQR) 4 (3.5–5) 4 (3.5–5) 4 (3–5) ISS, median (IQR) 26 (17.5–35) 26 (17–35) 29 (25–41) ATI, median (IQR) 25.5 (12.5–35.5) 26 (13–37) 20 (12–35) Abdominal damage control Liver, n (%) 25 (48.1%) 13 (48.1%) 12 (48.0%) Major vascular, n (%) 39 (75.0%) 20 (74.1%) 19 (76.0%) Hollow viscus, n (%) 33 (63.5%) 17 (63.0%) 16 (64.0%) Other, n (%) 38 (73.1%) 23 (85.2%) 15 (60.0%) Extraabdominal damage control, n (%) 46 (88.5%) 25 (92.6%) 21 (84.0%) Abdominal closure Commercial, n (%) 47 (90.4%) 25 (92.6%) 22 (88.0%) Barker, n (%) 5 (9.6%) 2 (7.4%) 3 (12.0%) PRBC, first 6 h, median (IQR) 4 (2–6) 4 (3–6) 4 (2–6) NS normal saline; HS hypertonic saline; SD standard deviation; IQR interquartile range; RTSt revised trauma score, used for triage; RTSt revised trauma score, used for survival calculation; ISS injury severity score; ATI abdominal trauma index; PRBC packed red blood cells associated trauma, the technique used for the abdomi- balance during the first 72 h occurred in both groups and nal wall closure, or the transfusions required (Table 1). was slightly higher in the NS group (0.29) (Table 3). Of the 27 patients randomized to the NS group, three The serum concentration of sodium was higher in the died before the 7th day and could not be analyzed for HS during the study. Table 2 shows the peak concentra- the primary endpoint, and one was sent to another hos- tion on day 3 which was 141 versus 157, p < 0.001. The pital on day eight and could not be analyzed for 28-day rate of hypernatremia was significantly higher in the mortality. Of the 25 subjects assigned to the HS group, HS group. While one episode of hypernatremia (3.7%) one died in the first week and could not be analyzed for occurred in the group of NS, 11 (44%) were observed in the primary outcome. the group of HS p < 0.001. Similarly, serum osmolality Of the 24 patients on the NS analyzed for abdominal on day three was higher in the HS group (Table 3). The closure, 17 (70.8%) were closed during the first seven median (IQR) of the number of ICU-free days was 16 days. Of the 24 on the HS, 19 (79.2%) were closed in (1–23) in the NS group and 19 (11–24) in the HS group the same period. This difference was not significant (p = 0.57). (p = 0.71) (Table 2). Survival analysis confirmed the absence of difference between groups (p = 0.559) Early termination of the clinical trial (Fig. 2). After recruiting the first 50 cases, an independent stat- As shown in Table 2, 28-day mortality was 11.5% in istician performed the first interim analysis. A power the NS group and 8.5% in the HS group (p = 1.00). The of 0.09 was found, and a conditional power of 0.34 number of patients with a SOFA score > 6 and the SOFA was calculated for the planned sample size. The 95% values were similar among both groups (p 0.32 and 0.95, CI for the RR at this level would have been 0.99–1.27. respectively) (Table 2). Five patients in each group expe- The recalculation of the sample size at the same p and rienced an increase in serum creatinine (0.17). Positive power, with the observed parameters, resulted in 1102 García et al. World Journal of Emergency Surgery (2023) 18:4 Page 6 of 10 Table 2 Hypertonic saline after a damage control laparotomy. Randomized controlled clinical trial. Outcomes Outcome NS HS p Abdominal closure in the first 7 days, n (%) 17/24 (70.8%) 19/24 (79.2%) 0.711 Day 28 mortality, n (%) 3/26 (11.5%) 2/24 (8.0%) 1.002 Abdominal compartment syndrome, n (%) 0 (–) 2 (8.0%) 0.272 Total SOFA score 5 (7.5–9) 6 (4–14) 0.953 Number of subjects with SOFA score > 6, n (%) 13 (59.1%) 12 (48.0%) 0.321 ICU-free days in the first 30 days, median (IQR) 16 (1–23) 19 (11–24) 0.573 Fluid balance Day 1, c.c., median (IQR) 2165 (1180–4119) 1828 (427–3344) 0.213 Day 2, c.c., median (IQR) 678 (106–1599) 387 (− 125–1165) 0.583 Day 3, c.c., median (IQR) 261 (− 32–950) 170 (− 136–580) 0.433 First 72 h, c.c., median (IQR) 3957 (1767–5946) 2486 (650–5578) 0.293 NS normal saline HS hypertonic saline IQR interquartile range 1 Chi2 2 Fisher’s Exact test 3 Wilcoxon–Mann–Whitney Fig. 2 Kaplan–Meier curve for the probability of abdominal wall closure over time patients. With this information and the observation of Discussion a high proportion of patients developing hypernatremia In this randomized clinical trial, which was stopped in one of the groups, the data and safety monitoring early for futility, hypertonic saline neither improved board recommended stopping the trial. primary fascial closure rates nor the time to it after DCL; however, it did increase the sodium concen- trations and was associated with a higher rate of García et al. World Journal of Emergency Surgery (2023) 18:4 Page 7 of 10 Table 3 Hypertonic saline after a damage control laparotomy. Randomized controlled clinical trial. Security items Variable NS HS p Fluid balance Day 1 2665.5 (678–261) 1828 (427–3344) 0.213 Day 2 768 (106–1599) 387 (− 125–1165) 0.583 Day 3 261 (− 32–950) 170 (− 136–580) 0.433 Day 4 357 (− 280–729) 10 (− 811–557) 0.193 Day 5 51.5 (− 1835–697) 133 (− 713–1101) 0.373 Day 6 − 385 (− 1057–140) 60 (− 1200–580) 0.373 Day 7 − 110 (− 1109–597) 267 (− 650–810) 0.683 First 72 h 3957 (1767–5976) 2486 (650–5578) 0.293 First 7 days 2998 (1278–6964) 3133 (− 1700–6603) 0.493 Sodium concentration Day 0 140 (138–143) 141 (139–142) – Day 1 140 (138.5–142) 148 (144.5–151) < 0.0013 Day 2 140 (138–143) 153 (150–157) < 0.0013 Day 3 141 (139–144) 157 (149–161) < 0.0013 Day 4 143 (140–146) 156 (146–160) < 0.0013 Day 5 143.5 (140–147) 151 (144–156.5) 0.0063 Day 6 144 (139–147) 149 (144–155) 0.0313 Day 7 144 (140–147) 143 (140–147) 0.953 Chloride concentration Day 0 105 (104–106) 106 (102–110) 0.653 Day 1 105 (103–107) 114.5 (110.5–120.5) < 0.0013 Day 2 107 (104.5–108.5) 120 (116–128) < 0.0013 Day 3 106.5 (105–111) 124 (111–127) < 0.0013 Day 4 107.5 (104–112) 122 (111–127) < 0.0013 Day 5 106 (103–110) 115 (108–122) 0.0083 Day 6 108 (104–113) 113 (107–117) 0.083 Day 7 107 (105–112) 108.5 (104–113) 0.583 Osmolality Day 0 299 (297–306) 306 (300–316) 0.033 Day 3 297.5 (290–305) 324 (308–333) 0.0013 Number of subjects with SOFA score > 6, n (%) 13 (59.1%) 12 (48.0%) 0.321 RIFLE score Serum creatinine increase > 50% 3 2 0.172 Serum creatinine increase > 100% 2 0 Serum creatinine increase > 200% 0 3 ICU-free days in the first 30 days, median (IQR) 16 (1–23) 19 (11–24) 0.573 NS normal saline; HS hypertonic saline; IQR interquartile range 1 Chi2 2 Fisher’s exact test 3 Wilcoxon–Mann–Whitney hypernatremia. This is, to our knowledge, the first ran- In line with the present results, the existing body of domized trial assessing the effect of infusing hypertonic research on hypertonic solutions for trauma resuscita- saline solution on injured patients undergoing damage tion has not been able to find survival benefits or con- control laparotomy. The findings contradict previous sistent beneficial effects with the use of hypertonic saline observational studies that posed hypertonic saline solu- in injured patients. Moreover, such as in this trial, pre- tion as an intervention associated with higher fascial vious resuscitation studies assessing the use of hyper- closure rates in DCL patients [6–8]. tonic solutions in trauma patients were halted due to García et al. World Journal of Emergency Surgery (2023) 18:4 Page 8 of 10 futility [25–27]. For example, two previous large trials accompanying peril of acute dysnatremias, which in funded by the National Heart, Lung, and Blood Institute turn can lead to serious adverse events, and the well- (NHLBI) [25–27], investigating the effect of HS adminis- known documented harms that the use of HS poses to tered during the prehospital resuscitation were stopped trauma patients [5], we do not recommend its use in early because interim analyses demonstrated insufficient the setting of injured patients undergoing damage-con- promise of an HS treatment benefit. Of concern, in one trol laparotomy. of these trials, an increase in mortality was found with Although this trial did not show positive results HS (Table 4). favoring HS, it might be possible to use it as a part of a A relatively small body of literature is concerned with bundle in future investigations. For example, in combi- the safety and effectiveness of HS after emergent lapa- nation with a mesh-mediating traction system, which rotomy. A seminal study in this area is the work of Har- (by itself ) has shown promising results, allowing a safe vin et al. [8], which showed that using 3% HS increased early abdominal closure [28]. For example, Alsaadi et al. the fascial closure rate and decreased the time to fascial [29] reported a series of 24 patients requiring emergency closure compared to the standard saline solution (early laparotomy in whom prophylactic onlay mesh was used. primary fascial closure: 78% in the NS group vs. 100% in They found that this intervention was associated with the HS group, p = 0.01). Building upon this study, Loftus acceptable wound-healing outcomes and recommended et al. [6, 7] published two studies that reported higher fas- it as a potential intervention to prevent fascial dehiscence cial closure rates with implementing a treatment bundle in injured patients. (including 3%-HS) for trauma patients requiring DCL. More broadly, research is also needed to determine In these studies, patients resuscitated with 3%-HS were the role and effects of direct peritoneal resuscitation on more likely to achieve early fascial closure; thus, provid- post-DCL outcomes. To date, studies on direct peritoneal ing evidence to underpin the implementation of trauma resuscitation have been performed primarily on animals resuscitation protocols including 3%-HS as a smooth [30], and little is known about its effect on clinically rel- path to achieve fascial closure in patients undergoing evant outcomes. One randomized trial [31], including DCL. The present randomized controlled trial results 52 patients undergoing damage control surgery, found challenge previous observational studies and should be that patients randomized to peritoneal resuscitation used as a source to develop clinical recommendations had higher rates of abdominal wall closure with reduced and implement changes in surgical practice. times to it, and lower rates of intra-abdominal infections. In the present trial, patients randomized to 3% HS had Therefore, if the debate about DCL and post-op care a significantly higher sodium concentrations and were after abdominal trauma is to be moved forward, a bet- more likely to present hypernatremia. These findings ter understanding of bundles, including direct peritoneal are broadly consistent with the work of other studies in resuscitation and mesh traction systems (through well- this area linking hypertonic saline infusion with hyper- designed clinical studies), needs to be developed [28]. natremia. For example, Loftus et al. [6, 7] showed that among patients undergoing emergent laparotomy and temporary abdominal closure, those resuscitated with Limitations hypertonic saline had a significantly higher sodium con- Our study has limitations. First, the small number of centration at 48 h following index laparotomy. patients available for analysis limits the results’ general- The findings presented in this randomized con- izability despite the randomization. Second, one of the trolled trial do not support the recommendation to most obvious shortcomings of this study is its potentially use hypertonic saline solution to achieve a favorable limited external validity derived from its single-center outcome regarding abdominal fascial closure. Moreo- nature. Third, related to its low sample size, the trial cer- ver, given the evident uncertainty of benefits with the tainly had a likelihood of type II error (declaring no dif- ferences between groups when, in fact, these differences exist). Thus, it could be argued that the study lacks suf- Table 4 Hypertonic saline after a damage control laparotomy. Randomized controlled clinical trial. Episodes of ficient power and should be interpreted as presenting hypernatremia >159 Meq/Ll inconclusive findings. However, we have presented the steps we followed to stop the trial, suggesting that com- Variable NS HS pleting the sample size would not have guaranteed reach- During the infusion 0 10 ing statistical significance. After the infusion 1 1 Total 1 11 NS normal saline HS hypertonic saline García et al. World Journal of Emergency Surgery (2023) 18:4 Page 9 of 10 Conclusion 11 Present Address: Department of Surgery, Universidad Sanitas, Bogotá, Colombia. This randomized clinical trial showed no benefit of hypertonic saline solution in primary fascial closure Received: 10 November 2022 Accepted: 4 January 2023 rates. Patients randomized to HS had higher sodium concentrations after the first day and were more likely to present hypernatremia. We do not recommend using HS in patients undergoing damage control laparotomy. References 1. Holcomb JB, Jenkins D, Rhee P, Johannigman J, Mahoney P, Mehta S, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma Acute Care Surg. 2007;62:307–10. Abbreviations 2. Cannon JW, Khan MA, Raja AS, Cohen MJ, Como JJ, Cotton BA, et al. Dam‑ DCL Damage control laparotomy age control resuscitation in patients with severe traumatic hemorrhage: HS Hypertonic saline a practice management guideline from the Eastern Association for the NS Normal saline Surgery of Trauma. J Trauma Acute Care Surg. 2017;82:605–17. 3. Godat L, Kobayashi L, Costantini T, Coimbra R. Abdominal damage Acknowledgements control surgery and reconstruction: world society of emergency surgery The authors of this manuscript want to thank the Clinical Research Center staff position paper. World J Emerg Surg. 2013;8:53. for their constant support. 4. Kramer GC. Hypertonic resuscitation: physiologic mechanisms and recommendations for trauma care. J Trauma. 2003;54:S89-99. Author contributions 5. Patanwala AE, Amini A, Erstad BL. Use of hypertonic saline injection in Trial design: AFG, GAOT, and JCP. Writing of the trial protocol: AFG. Screening, trauma. Am J Heal Pharm. 2010;67:1920–8. randomization, and follow-up of the patients: MPN, JCY, JGB, and RMN. Statisti‑ 6. Loftus TJ, Efron PA, Bala TM, Rosenthal MD, Croft CA, Smith RS, et al. cal analyses: AFG and AIS. Critical evaluation of the results: AFG, DCC, AIS, JHM, Hypertonic saline resuscitation after emergent laparotomy and tempo‑ GAOT, CAO, and JCP. Writing of the first draft of the manuscript: AFG and RMN. rary abdominal closure. J Trauma Acute Care Surg. 2018;84:350–7. All authors made relevant intellectual contributions to the manuscript, and all 7. Loftus TJ, Efron PA, Bala TM, Rosenthal MD, Croft CA, Walters MS, et al. The authors approved the final version for journal submission. All authors read and impact of standardized protocol implementation for surgical damage approved the final manuscript. control and temporary abdominal closure after emergent laparotomy. J Trauma Acute Care Surg. 2019;86:670–8. Funding 8. Harvin JA, Mims MM, Duchesne JC, Cox CSJ, Wade CE, Holcomb JB, et al. The author(s) received no financial support for the research, authorship, and/ Chasing 100%: the use of hypertonic saline to improve early, primary or publication of this article. fascial closure after damage control laparotomy. J Trauma Acute Care Surg. 2013;74:422–6. Availability of data and materials 9. 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Smith JW, Matheson PJ, Franklin GA, Harbrecht BG, Richardson JD, Garri‑ son RN. Randomized controlled trial evaluating the efficacy of peritoneal resuscitation in the management of trauma patients undergoing dam‑ age control surgery. J Am Coll Surg. 2017;224:396–404. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in pub‑ lished maps and institutional affiliations. Ready to submit your research ? Choose BMC and benefit from: • fast, convenient online submission • thorough peer review by experienced researchers in your field • rapid publication on acceptance • support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations • maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions