|Year : 2021 | Volume
| Issue : 3 | Page : 134-138
Plasmalyte versus normal saline as resuscitation fluid in children: A randomized controlled trial
Vandana Arya, M Kavitha, Kundan Mittal, Virender Kumar Gehlawat
Department of Pediatrics, Pt. BD Sharma PGIMS, Rohtak, Haryana, India
|Date of Submission||11-Feb-2021|
|Date of Decision||09-Apr-2021|
|Date of Acceptance||16-Apr-2021|
|Date of Web Publication||21-May-2021|
Dr. Kundan Mittal
Department of Pediatrics, Pt. BD Sharma PGIMS, Rohtak - 124 001, Haryana
Source of Support: None, Conflict of Interest: None
Background: Plasmalyte A, a balanced solution is reported to be associated with a reduced incidence of hyperchloremia and metabolic acidosis when compared with 0.9% NaCl among adults. Considering the paucity of evidence in the pediatric population, the present study was conducted with an objective to compare the efficacy and safety of plasmalyte and normal saline as intravenous fluid bolus therapy in children with shock in terms of Electrolytes and Acid-base balance at admission and at 6 h.
Subjects and Methods: This double-blinded, randomized controlled trial was conducted in the pediatric emergency department (ED) of a tertiary care hospital among children aged 1 month to 14 years who presented to the ED with shock. A total of 400 children were randomized to receive either plasmalyte or 0.9% saline solution as intravenous fluid bolus therapy. Changes in laboratory parameters including pH, serum bicarbonate levels, serum lactate level, and serum electrolytes-sodium, potassium, chloride levels from baseline (hour 0) to hour 6 were compared in both groups. Secondary outcomes included the need for vasopressors, duration of hospital stay, and in-hospital mortality.
Results: The two groups were similar in terms of baseline clinical characteristics. Patients receiving plasmalyte demonstrated significantly greater improvement in the pH (P = 0.001), bicarbonate (P = 0.001) and lactate levels (P = 0.03) compared with patients receiving normal saline. In addition, normal saline group patients had a higher rise in sodium (P = 0.11) and chloride levels (P = 0.02) as compared to the plasmalyte group. The children who received plasmalyte had a significantly lesser need for vasopressors (P = 0.04), shorter mean duration of hospital stay (P = 0.01), and lower mortality (P = 0.03).
Conclusion: Plasmalyte was superior to Normal saline when used as a resuscitation fluid in children with shock, in terms of better improvement of acid-base balance after fluid bolus therapy, a lower rise in serum chloride level at 6 h from baseline, shorter hospital stay, lesser need for vasoactive drugs and lower mortality.
Keywords: Normal saline, plasmalyte, shock
|How to cite this article:|
Arya V, Kavitha M, Mittal K, Gehlawat VK. Plasmalyte versus normal saline as resuscitation fluid in children: A randomized controlled trial. J Pediatr Crit Care 2021;8:134-8
|How to cite this URL:|
Arya V, Kavitha M, Mittal K, Gehlawat VK. Plasmalyte versus normal saline as resuscitation fluid in children: A randomized controlled trial. J Pediatr Crit Care [serial online] 2021 [cited 2023 Feb 8];8:134-8. Available from: http://www.jpcc.org.in/text.asp?2021/8/3/134/316591
| Introduction|| |
The initial step in the management of most of the shock patients is fluid resuscitation. The choice of fluid has always remained a matter of debate. Initially, it was centered around the choice between colloid versus crystalloid solutions. Out of these two, crystalloids are often the preferred solutions as there is little or no difference in efficacy,,, are relatively cheap, easily available, easily storable and have a good shelf life. Moreover, there is less allergy risk associated with the use of crystalloids.
As per the Pediatric Advanced Life Support guidelines, shock in children should be treated with isotonic crystalloids (normal saline or balanced crystalloids). However, there is a lack of evidence to recommend one isotonic crystalloid over another in children. Normal saline is still the mainstay of fluid resuscitation and is the most widely used fluid worldwide. However, normal saline is not really normal as it contains supraphysiologic chloride concentration and its use has been found to be associated with hyperchloremic acidosis, nephrotoxicity, and increased mortality.,,
Plasmalyte A (PLA, Baxter Healthcare, Deerfield, IL), a balanced isotonic crystalloid, contains physiologic sodium, chloride, potassium, magnesium, and bicarbonate precursors in mEq/L: Na 140, K 5, Cl 98, Mg 3, Acetate 27, and gluconate 23 and a pH of 7.4. It is utilized as a source of water and electrolytes or as an alkalinizing agent. In addition to the physiologic chloride level, Plasmalyte A contains acetate and gluconate, which serve as buffering agents. Several studies in adults have reported a reduction in the incidence of hyperchloremia and metabolic acidosis with balanced solutions (Lactated Ringers or Plasmalyte A) over 0.9% NaCl.,, However, there is the paucity of evidence in the pediatric population comparing the clinical outcome and adverse effects related to the use of normal saline versus balanced solutions like plasmalyte.
The hypothesis of this study was that plasmalyte would be superior to normal saline as an initial resuscitation fluid in the treatment of children with shock in terms of electrolytes and Acid-base balance at admission and at 6 h and results in less mortality and a shorter mean duration of hospital stay.
| Materials and Methods|| |
This double-blinded, randomized controlled trial was conducted in the pediatric emergency department (ED) of a tertiary care hospital in Northern India for 1 year (CTRI/2018/05/013995). Children aged 1 month to 14 years who presented to the ED with shock were eligible for enrollment. Shock was recognized clinically by the presence of one or more of: Tachycardia, weak peripheral pulses, cold extremities, slow capillary refill >2 s, systolic blood pressure <2 standard deviation (SD) below normal for age, decreased urine output, or altered consciousness. Children with chronic health conditions such as chronic kidney disease, congestive heart failure, DKA were excluded from the study. A feasibility sample size of 400 (200 in Group A and 200 in Group B) was taken. The institutional ethics approval was obtained and written informed consent was obtained from the parent or guardians of all participants.
Baseline data including demographic data, history, and examination findings were recorded. Randomization was done using the computer-generated randomized sequence and sealed envelopes were used for concealed allocation of the eligible patients to receive either plasmalyte or 0.9% NaCl as bolus therapy. Opaque wrappers were placed around the iv fluid bags and labeled them as “Study fluid A” and “Study fluid B” with expiry date by two staff nurses who were not involved in the study any further. The treating pediatrician at ED and principal investigator remained blinded to the study interventions until all enrolled patients followed up and the final analysis was executed. Following randomization, hour zero (baseline) was defined as the beginning of infusion of the first bolus of blinded study treatment in a dose of 10 ml/kg by gravity method over approximately 10 min. The patients were monitored continuously and reassessed after each bolus for the need for repeat boluses or vasopressors. Safety assessments included signs of fluid overload (e.g., worsening respiratory distress, new or worsening oxygen requirement, rales, gallop rhythm, or hepatomegaly), worsening of laboratory parameters from baseline, and any reported or observed adverse events. No change to the trial protocol or outcome had occurred after the study was commenced. The primary outcome was the change in the pH, serum bicarbonate levels, serum lactate level (mmol/L), and serum electrolytes-sodium, potassium, chloride (mEq/L) from baseline (hour 0) to hour 6. Secondary outcomes included the need for vasopressors, duration of hospital stay, and in-hospital mortality.
At the end of the study, the data were collected and analyzed using IBM SPSS Statistics Version 22.0. For descriptive statistics frequencies, percentages, mean and SD of different variables were calculated. For comparison of qualitative data, Chi-square test was used and for quantitative data, independent t-test was used. The P value was two-tailed and the probability level of significant difference was set at P ≤ 0.05.
| Results|| |
A total of 468 patients who presented to the pediatric ED in shock were screened for inclusion in this trial. After exclusion, 400 patients underwent randomization and received either normal saline or plasmalyte as bolus therapy (200 in each group) [Figure 1]. The two groups were similar in terms of patient demographics and baseline characteristics [Table 1].
The change in the pretreatment laboratory parameters and 6 h values in the plasmalyte and the normal saline group are presented in [Table 2] and [Table 3], respectively. In the plasmalyte group, there were a significant improvement in the pH, serum bicarbonate, and serum lactate levels over a period of 6 h, although there was no significant change in serum electrolyte levels [Table 2]. The children who received normal saline as fluid bolus also showed a statistically significant improvement in the acid-base status, but, moreover, they had a significant rise in the serum sodium and the serum chloride levels [Table 3].
|Table 2: Comparison of laboratory investigations (baseline vs. 6 h) in Group A (plasmalyte) (n=200)|
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|Table 3: Comparison of laboratory investigations (baseline vs. 6 h) in Group B (normal saline) (n=200)|
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The outcome comparisons between the two groups are presented in [Table 4]. Patients receiving Plasmalyte demonstrated significantly greater improvement in the pH, bicarbonate, and lactate levels compared with patients receiving normal saline. In addition, normal saline group patients had a significantly higher rise in chloride levels as compared to the other group. The children who received Plasmalyte had a significantly lesser need for vasopressors, shorter mean duration of hospital stay, and lower mortality.
|Table 4: Laboratory and clinical outcomes among children receiving plasmalyte versus normal saline|
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| Discussion|| |
This prospective randomized trial comparing plasmalyte to 0.9% saline as fluid bolus therapy in children presenting with shock determined that plasmalyte was superior to 0.9% saline in improving the metabolic acidosis and lowering the serum lactate level. Moreover, plasmalyte use was found to be associated with a significantly lower rise in serum chloride levels as compared to normal saline.
Among adults, several studies have compared the use of normal saline and balanced solutions in different settings like for initial resuscitation in trauma patients, as intraoperative fluid replacement, as resuscitation fluid in diabetic ketoacidosis patients and have reported a higher incidence of metabolic acidosis and hyperchloremia in patients who received saline compared with balanced solutions. A randomized, controlled, double-blinded crossover study on the effects of 2 L infusion of NS and PL on renal blood flow velocity and renal cortical tissue perfusion on healthy volunteers showed NS was associated with hyperchloremia (P < 0.0001) and metabolic acidosis (P < 0.025), a reduction in mean renal artery flow velocity (P = 0.045) and renal cortical tissue perfusion (P = 0.008). Recent large, randomized controlled trials done in both critically ill and noncritically ill adults showed that the use of balanced crystalloids for intravenous fluid administration appeared to reduce the composite outcome of in-hospital mortality, new renal replacement therapy, and persistent renal dysfunction compared with the use of saline., However, some studies aiming to determine the effects of these two fluids on renal complications and mortality did not show any significant difference in the clinically relevant endpoints.,
There are surprisingly few trials examining fluid resuscitation strategies in children. The recommendations are based on consensus or expert opinion rather than results of definitive studies or meta-analysis. There are studies comparing hypotonic and isotonic crystalloids, showing that isotonic crystalloids protect against hyponatremia. But only limited data are available comparing balanced crystalloids with normal saline. Allen et al. conducted a prospective, randomized, double-blind, multicenter trial comparing Plasmalyte and 0.9% sodium chloride in children with moderate to severe dehydration secondary to acute gastroenteritis and found that Plasmalyte was superior to normal saline in improving the metabolic acidosis (change in bicarbonate from baseline of 1.6 mEq/l for PL versus 0.0 mEq/L for NS) despite comparable initial serum bicarbonate levels and dehydration score also significantly improved at hour 2 in patients receiving plasmalyte. In our study, about 60% of the patients had acute gastroenteritis as the underlying illness and presented with shock. Although no stratified analysis was done in these patients.
Lima et al. studied balanced crystalloids and saline for perioperative fluid administration in children undergoing neurosurgery and found that saline infusion increased variation in serum chloride levels and also resulted in a higher incidence of hyperchloremic metabolic acidosis. Similar findings of saline being associated with a higher rise in chloride levels were observed in the present study also.
Hyperchloremia has been shown to be linked with adverse clinical outcomes in several animal and human studies. McCluskey et al. reviewed the datasets of 22851 surgical patients and determined that hyperchloremia was associated with adverse renal outcomes and 30-day mortality. A study done in healthy volunteers has shown that hyperchloremia produces renal vasoconstriction and results in reduced renal cortical tissue perfusion. Similar association is seen in the pediatric population also. In a large cohort study evaluating 890 children with septic shock from 29 pediatric intensive care units (PICUs) in the USA, it was found that minimum chloride level >110 mmol/l had higher odds of a complicated course and increased mortality.
Our study subjects were children who presented with shock and required fluid boluses. Very limited data is available comparing the efficacy and safety profile of different crystalloids in this population. A large retrospective study compared balanced and unbalanced fluids in 36,908 PICU patients aged 0–18 years diagnosed with severe sepsis and found lower mortality at 72 h, lower AKI prevalence, and fewer days on vasoactive drugs in the balanced fluid group. These findings are consistent with our study findings of lower mortality and lesser need for vasoactive drugs in patients who received plasmalyte.
The present study is one of the few clinical trials comparing normal saline and plasmalyte in children and provides robust evidence in favor of plasmalyte as one of the balanced crystalloids with a potential for a better outcome in children with shock. The strengths of this study are its randomization, effective blinding, and clinical equipoise. However, there are some shortcomings of our study. Patient evaluation based on type of shock (e.g., hypovolemic, septic shock), presence of malnutrition, or presence of acute kidney injury was not done. Considering these confounders, further studies may be conducted on larger scales for further evaluation of the optimal fluid to use in the resuscitation of pediatric patients with shock.
| Conclusion|| |
Plasmalyte was superior to normal saline when used as a resuscitation fluid in children with shock, in terms of better improvement of acid-base balance and a lower rise in serum chloride level at 6 h from baseline. The children who received plasmalyte had a shorter hospital stay, lesser need for vasoactive drugs, and lower mortality.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]