Comparative evaluation of intraoperative use of normal saline, Ringer's lactate, and combination of normal saline and Ringer's lactate in neurosurgical patients – A preliminary randomized clinical trial
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.258047
Source of Support: None, Conflict of Interest: None
Keywords: Intraoperative fluid management, neurosurgery, normal saline, Ringer's lactate
Intraoperative fluid management is of significant concern in patients undergoing neurosurgery. The goals of intraoperative fluid management in neurosurgical patients would be to maintain fluid, electrolyte, and metabolic balance. Concurrently, it is important to avoid any brain edema and rise in intracranial pressure (ICP). The common fluids used in patients undergoing neurosurgical procedures are crystalloids. There is a wide variability with regard to the choice of crystalloids in neurosurgical patients based on either institutional practice or personal experience.
Normal saline (NS) is a relatively hypertonic solution when compared with plasma. It may have an advantage in neurosurgical patients with raised ICP. However, using a large volume of NS in moderate to prolonged surgical procedures has the risk of inducing hyperchloremic metabolic acidosis. Ringer's lactate (RL) is a balanced intravenous solution which has been described to maintain the internal milieu of the intravenous compartment. What can place RL at a disadvantage during intracranial surgery is the fact that it is constitutionally a hypotonic solution with the risk of rise in ICP., Yet, there are few physicians, who use a combination of NS and RL with the belief that it will maintain the serum osmolarity and at the same time overcome the disadvantages that accompany the use of particular crystalloids solutions when used alone. Glucose-containing solutions have to be avoided as a routine for neurosurgical procedures due to the risk of inducing hyperglycemia and thereby exacerbating any consequences related to cerebral ischemia.,,,
Underlying all the physiological assumption and the beliefs of our practice is a lack of clinical evidence as to what would actually benefit the patients undergoing neurosurgery. This study was designed with the objective to compare the use of NS, RL, or their combination in determining the outcome in patients undergoing intracranial tumor surgery. The effects of the fluids on serum electrolytes, metabolic (acid–base) balance, intraoperative hemodynamics, brain relaxation, and duration of postoperative hospital stay were the outcome parameters of the study.
This study was a prospective randomized clinical trial conducted between August 2007 and August 2015 at the Neurosciences Centre of All India Institute of Medical Sciences, New Delhi. Ethical approval for the conduct of the study was obtained from the human research committee of the institute. This trial has been registered with the National Clinical Trials Registry.
A total of 90 patients who were scheduled to undergo elective supratentorial and infratentorial tumor surgery were included in the study after obtaining a written informed consent. There is no similar study in the literature evaluating the outcome with crystalloids in neurosurgical patients. Consequently, this study was carried out as a preliminary trial with 30 patients in each group. Patients who had hypertension, diabetes mellitus, endocrinological dysfunction, as well as cardiac, respiratory, or renal diseases were excluded from the study. Patients who did not have a full score on the preoperative Glasgow Coma Scale (GCS) assessment or those undergoing a second intracranial procedure were not included in the study.
Randomization and masking
The patients were equally randomized to one of the three intraoperative fluid protocols. The randomization was done using computer-generated random numbers and allocated to one of the study groups on the morning of surgery using a sealed opaque envelope. All the patients, surgeons, nurses, laboratory technicians, and data recorders involved in the study were blinded to the fluid administered.
The staff nurse in charge of the operation theater who was not aware of the study protocol opened the envelope and supplied the fluids prepared by the hospital pharmacy in identical 500-mL glass bottles as per the allocated group. Two intravenous ports were used to administer the intravenous fluids. The patients of NS group received only NS, whereas the patients of RL group received only RL as crystalloids. In the NS+RL group, one intravenous port was used to administer NS and the other for administration of RL. The NS+RL group received a combination of NS and RL in equal quantity with a maximum difference of 250 mL. The attending anesthesiologist was aware of the fluid being administered. However, the identity of the intraoperative fluids given was concealed from the patients, surgeons, nurses, and laboratory technicians involved in the study. The intraoperative fluid requirements and administration of blood, blood products, and colloids were at the discretion of the attending anesthesiologist. Postoperative fluid management was at the discretion of the postoperative care providers.
The preoperative radiological scans were evaluated. The tumor location, nature of the lesion, maximum tumor diameter, and features of preoperative raised intracranial pressure (ICP) as evidenced by the presence of peritumoral edema, mass effect, and/or hydrocephalus were noted. Intraoperative monitoring consisted of five-lead electrocardiography, pulse oximetry, capnography, invasive blood pressure, central venous pressure (CVP), end-tidal anesthetic gases, and neuromuscular blockade assessment. The anesthesia technique was similar in all the patients. All the patients were induced with fentanyl 2 μg/kg and thiopentone sodium 4–6 mg/kg. Tracheal intubation was facilitated with rocuronium 1 mg/kg. Anesthesia was maintained with isoflurane and nitrous oxide in oxygen (60:40) to maintain a combined minimal alveolar concentration of 0.8–1.1. Vecuronium was administered for muscle relaxation to maintain less than two twitches on neurostimulation. Additional boluses of fentanyl were used as per the need. About 0.5–1 g/kg of mannitol was given to all the patients at the time of skin incision as per the institutional protocol. The surgeries were performed by senior and experienced neurosurgeons. Following completion of surgery, the decision for tracheal extubation was at the discretion of the attending anesthesiologist in consultation with operating neurosurgeon. The patients were then shifted to the neurosurgical intensive care unit for immediate postoperative management and subsequently to the surgical ward.
The laboratory parameters were estimated using the FLEX Radiometer 800 arterial blood gas analyzer. The electrolytes estimated and recorded were serum sodium, serum potassium, serum calcium, and serum chloride along with calculated serum osmolarity. The metabolic parameters included arterial blood pH, arterial bicarbonate, base deficits, lactates, and blood glucose. Hemodynamic variables were continuously monitored intraoperatively and included the heart rate (HR), mean arterial blood pressure (MAP), and central venous pressure (CVP). The preinduction HR and MAP were noted with the patient lying undisturbed in the operation theater. The mean of the three recordings were taken as the baseline HR and MAP. The baseline CVP measurements were recorded after central venous cannulation following the induction of anesthesia. The hemodynamic and laboratory parameters were recorded at the following time points for all the patients: (1) preinduction (baseline), (2) postinduction, (3) skin incision, (4) bone flap elevation, (5) tumor resection, (6) skin closure, (7) emergence from anesthesia, (8) first postoperative hour, and (9) first postoperative day. The brain relaxation score was reported by the attending neurosurgeon following elevation of the bone flap. It was graded as relaxed, mild bulge, moderate bulge but could be managed, or severe bulge which needed an intervention. The postoperative hospital stay as a surrogate marker of morbidity was the other outcome parameter of the study. It was defined as the duration of stay in the hospital following surgery before the patient was discharged home. The criteria for discharge of patients were neurological stability (no alteration in the Glasgow Coma Scale (GCS) for 5 successive days), hemodynamic stability, spontaneous breathing, the ability to maintain oxygen saturation >95% on room air, accepting feeds either orally or through the nasogastric tube, and ensuring that the patients were free of any infection. The factors that could influence the postoperative hospital stay such as new-onset neurological deficits, convulsions, and fever (>38°C on two or more occasions) were also recorded. A neuroanesthesia senior resident who was blinded to the intraoperative fluids protocol recorded the perioperative data.
Parametric data were compared between the groups using one-way analysis of variance (ANOVA), while post hoc analysis for the same data was done using a Bonferroni's correction. Nonparametric data were compared using Pearson's chi-square or Kruskal–Wallis test. Where needed, Fisher's exact test was applied. Post hoc analysis for this data was done through Mann–Whitney test by adjusting the level of significance. The biochemical, metabolic, and hemodynamic parameters between the groups were compared using two-way ANOVA. All calculations were two-sided and were performed using Statistical Package for Social Sciences (SPSS Inc., 2013, version 22.0 for Windows; Armonk, NY, USA). A P value less than 0.05 was considered statistically significant.
A total of 90 patients were enrolled in the study. Two patients from the NS and NS+RL groups and one patient from the RL group were excluded from the study [Figure 1]. The data were analyzed and compared for 28 patients in the NS group, 29 patients in the RL group, and 28 patients in the NS+RL group [Figure 1]. The demographic, preoperative, and intraoperative characteristics were similar among the three groups [Table 1] and [Table 2].
The serum osmolarity was significantly lower in the RL group when compared with the other two groups during bone flap elevation, following surgery, and in the postoperative period (P < 0.05). Similarly, the serum sodium levels were significantly lower in the RL group when compared with the other groups in the identical time periods [Figure 2]a. Significant hyperchloremia was observed with the use of NS when compared with the use of RL during the intraoperative period [Figure 2]b. Hyperchloremia was also significant with the use of combination fluid when compared with RL in the postoperative period [Figure 2]b. The ionized serum calcium levels were significantly lower in the NS group when compared with the other two groups at different time points [Figure 2]c. There was no significant difference in the potassium levels in the three groups [Figure 2]d.
Significant difference in the pH of arterial blood was observed with the use of NS when compared with the use of RL and the combination of NS+RL during the time when bone flap was raised and during tumor resection. The difference continued between NS and RL groups up to the first postoperative day [Figure 3]a. Significant acidosis (base deficits and decrease in HCO3−) was observed with the use of NS when compared with the use of RL and the combination of NS+RL intraoperatively and in the postoperative period [Figure 3]b and [Figure 3]c. The lactate levels were significantly higher with the use of RL when compared with NS during the intraoperative period [Figure 3]d. The blood glucose and hemoglobin levels were similar in all the groups at various time periods.
The intraoperative HRs were comparable among the three groups except following induction of anesthesia and bone flap reflection where patients of the NS group had significantly higher HRs [Figure 4]a. The MAP and CVP were similar among the three groups at various time points [Figure 4]b and [Figure 4]c. The patients of RL group had lower CVP at the time of emergence from anesthesia in comparison to the other two groups [Figure 4]c. The brain relaxation scores were comparable among the three groups at the time following the reflection of bone flap [Table 2].
The duration of postoperative hospital stay was comparable with the use of the three fluid protocols [Table 3]. Similarly, the length of stay in the intensive care unit (ICU) was also similar among the three groups. The incidence of postoperative convulsions, new-onset neurological deficits, and fever were also similar among the groups [Table 3].
Appropriate fluid management is one of the mainstays of anesthetic management of neurosurgical patients. The use of NS was associated with significant intraoperative hyperchloremic metabolic acidosis and ionic hypocalcemia. Significant hyponatremia and higher lactate levels were observed in patients who received RL. The electrolyte and metabolic parameters were usually well-preserved intraoperatively with the combination group of fluids. This study was designed to evaluate the effect of NS, RL and the combination of the two on biochemical and clinical outcomes in neurosurgical patients. The intraoperative hemodynamics and brain relaxation scores were also similar. The study did not observe any difference in the duration of hospital stay among the three groups.
Electrolyte balance is essential for maintenance of cerebral homeostasis. At the same time, electrolyte imbalance may reflect disruption of cerebral homeostasis in neurosurgical patients., Consequently, intravenous fluids should be evaluated for their effect on electrolyte balance. The use of RL was associated with significant hyponatremia and reduced osmolarity when compared with NS during elevation of bone flap and following completion of surgery. Intraoperative hyperchloremia and ionic hypocalcemia were observed in patients who received NS when compared with the RL group. The combination of NS+RL had the least effect on the electrolytes. The above observations with the use of NS or RL in our study are similar to the reports of previous studies., Despite the variable consequence of the different fluids on the electrolyte balance, we did not observe any difference in the overall clinical outcome of the patients.
An acid–base balance is essential for normal cellular function of the body. A disturbed acid–base balance reflects exhaustion of buffering actions of the body systems and may affect the neurological and cardiovascular functions of the body. The use of NS was associated with metabolic acidosis, as reflected by HCO3 and base deficits in the intraoperative and postoperative period. The acidosis was associated with hyperchloremia, which is a known entity with large volume NS infusion., However, this did not impact the neurological and cardiovascular functions as well as the overall outcome of the patients in our study. On the other hand, the use of RL was associated with significantly higher lactate levels when compared with the use of NS. The elevated lactate levels also did not influence the outcome in our patients. However, administration of RL to critically ill neurosurgical patients may be of concern as blood lactate concentration is used as a marker of hypoperfusion., The use of NS+RL had the least impact on the metabolic parameters of the patients. Notwithstanding the variable effects of the fluids on the metabolic parameters, there was no significant difference in the clinical outcome of the patients. Acidosis with a serum pH <7.2 has been observed to be associated with a poor outcome. The effect of the fluids on serum lactates, base deficits, and HCO3− in our study did not have a profound effect on the pH and consequently the outcome.
Stable intraoperative hemodynamics are imperative for the maintenance of cerebral perfusion. Hemodynamic parameters are dependent on the cardiac preload and myocardial contractility. NS has been reported to impact the urine output and intravascular volume., We did not observe any difference in the fluid requirements, CVP, or urine output in the three groups, thereby suggesting the ability of all the three fluid protocols in maintaining intravascular volume. Ionic hypocalcemia and acidosis observed in the NS group in our study have the potential to affect myocardial functions and hemodynamics. The impact of ionic hypocalcemia in hemodynamic changes is clinically evident at levels less than 0.65 mmol/L. Similarly, acidosis leading to a decreased cardiac output and hemodynamic compromise is observed when pH <7.2., The patients in the NS group in our study had both ionic calcium and pH well above the described limits. Consequently, despite the significant ionic hypocalcemia and acidosis in the NS group, there was no overbearing variation in the hemodynamic parameters when compared with the other two groups.
Facilitation of brain relaxation is desirable to allow an optimal surgical exposure for safe and maximal tumor resection. The observations of our study reflect that all the three fluid protocols were associated with acceptable brain relaxation. There is an inverse correlation between serum sodium concentration and ICP. Administration of large volume of RL has the potential to cause cerebral edema and raised ICP., During bone flap reflection, the patients of the RL group in our study had serum sodium levels and serum osmolarity which were significantly lower than those of patients who received NS. However, this did not translate clinically into greater brain swelling within the RL group or a better brain relaxation within the NS group. This could probably be related to the fact that all the patients in this study received mannitol intraoperatively and the calculated osmolarity in our study may not reflect the true osmolarity. The findings of our study are similar to that of Williams et al., who did not observe any clinically significant increase in ICP in healthy volunteers who received large volume infusion of NS or RL.
The duration of hospital stay was an important outcome parameter of our study. Enhanced recovery and reduced length of hospital stay are desirable in surgical patients. Intraoperative fluid management can influence the postoperative complications and duration of hospital stay. Our study did not observe any difference in the duration of hospital stay with the use of the three fluid protocols. The effect of intraoperative fluid administration on the perioperative metabolic and biochemical parameters in our study was only mild to moderate. Moreover, they did not have a significant influence on important clinical parameters such as intraoperative brain swelling and perioperative hemodynamics. Similarly, postoperative complications such as neurosurgical deficits, convulsions, and fever, which can prolong the hospital stay, were also comparable among the three groups. A meta-analysis of five trials by Cochrane collaborators compared the perioperative nonbuffered salt solution such as NS with the buffered fluid such as RL for the length of hospital stay in patients undergoing surgery. There was no significant difference in the length of hospital stay with the use of either fluid, a finding which is similar to our results.
This is a preliminary study and has limitations of its own. One of the major drawbacks of this study is that it includes all intracranial brain tumors. The outcome of patients with supratentorial and infratentorial tumors can be different. The study was partially blinded as the attending anesthesiologist was aware of the fluid protocol. The assessment of brain relaxation was subjective and monitoring of ICP would have been ideal. Despite the shortcomings, this is the first study which evaluates the effect of commonly used crystalloids in determining the outcome in patients undergoing neurosurgery. It is important to understand that this study was conducted in healthy patients undergoing elective neurosurgery. The result of this study cannot be extrapolated to neurosurgical patients who are critically ill or have deranged biochemical parameters as these fluids have the potential to influence the electrolyte and metabolic balance.
This study is a modest trial to evaluate the effect of the intraoperative use of NS, RL, or its combination on the outcome in patients undergoing elective neurosurgery. The use of NS is associated with hyperchloremic metabolic acidosis and ionic hypocalcaemia. RL infusion has the potential to cause hyponatremia and an increase in the lactate levels. The combination of NS and RL has the least influence on serum electrolytes and metabolic parameters. The data suggest that the all the three fluid protocols are similar in terms of overall clinical outcome in patients undergoing elective intracranial tumor surgery.
Financial support and sponsorship
Dr. Hemant Bhagat received fellowship from the Council of Scientific and Industrial Research (CSIR), New Delhi, for the. conduct of this study at the All India Institute of Medical Sciences, New Delhi.
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]