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ORIGINAL ARTICLE
Year : 2022 | Volume
: 8
| Issue : 4 | Page : 200-206
Comparison and evaluation of two different crystalloids - Normal saline and plasmalyte in patients of traumatic brain injury undergoing craniotomy
Renu Bala, Teena Bansal, Anshul Mundra, Kirti Kamal
Department of Anaesthesiology and Critical Care, Pt B D Sharma University of Health Sciences, Rohtak, Haryana, India
Correspondence Address:
Teena Bansal
19/6 J Medical Campus, PGIMS, Rohtak - 124 001, Haryana
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/bc.bc_54_22
BACKGROUND AND AIMS: Fluid therapy is one of the most important components of the management of patients with traumatic brain injury (TBI). The present study was planned to compare plasmalyte and normal saline (NS) in patients who underwent craniotomies for TBI in terms of their effects on acid–base equilibrium, renal functions, and coagulation profile.
METHODS: Fifty patients of age 18–45 years of either sex, who underwent emergency craniotomy for TBI, were included in the study. The patients were randomized into two groups. Group P (n = 25) received isotonic balanced crystalloid (plasmalyte) and Group N (n = 25) received NS intraoperatively and postoperatively till 24 h after surgery.
RESULTS: The pH was lower in Group N (P < 0.05) at different time points after surgery. Similarly, more patients in Group N had pH <7.3 (P < 0.05); while the rest of the metabolic parameters were comparable in the two groups. Blood urea and serum creatinine were higher in Group N. Coagulation profile was comparable in the two groups.
CONCLUSION: Acid–base, electrolyte balance, and renal profile were better in patients receiving plasmalyte as compared to NS. Hence, it can be a wiser choice for fluid management in patients of TBI undergoing craniotomy.
Keywords: Craniotomy, isotonic balanced crystalloid, normal saline, traumatic brain injury
Fluid therapy is one of the most important components of the management of patients with traumatic brain injury (TBI) as hypovolemia and hypervolemia both are detrimental to the brain. Not even the amount of fluid, but the type of fluid is also equally important in them. The main goals of fluid therapy are to optimize cerebral brain perfusion, maintain adequate cerebral oxygenation, and avoid cerebral edema.[1]
Normal saline (NS) is the most commonly used crystalloid in TBI patients as it is an isotonic solution related to plasma. However, it does not contain other electrolytes and has the potential to cause hyperchloremic acidosis. To circumvent all these problems, there is a need for a crystalloid which is isotonic to plasma, contains electrolytes in proper concentration, and is not likely to disturb the acid–base equilibrium.[2]
The isotonic balanced crystalloid (BC) (plasmalyte) is a relatively newer crystalloid. The corrected osmolality of plasmalyte solution is 273 mOsm/kg H2O. In addition, the pH of plasmalyte is approximately 7.4; however, it adjusts with sodium chloride and depends on country manufacturers ranging from 6.5 to 8. Although plasmalyte is not an isotonic crystalloid, is nearly the same as that of plasma. It has been compared with NS in several preoperative and perioperative settings such as resuscitation of trauma patients, diabetic ketoacidosis, renal transplant surgery, and hepatic, cardiac, and spine surgery. The investigators have reported its favorable profile in terms of acid–base balance and renal functions.[3],[4]
Neutrophil gelatinase-associated lipocalin (NGAL) is a proximal tubular injury biomarker. It has been shown to predict the risk of acute kidney injury (AKI) as early as within 6 h of a clinical insult. In contrast, conventionally employed biomarkers like serum creatinine start to rise 24–72 h after the injury has occurred, and also its values are affected by several other factors. Thus, NGAL may be used as a surrogate marker of AKI. Early detection of AKI may facilitate the institution of preventive or corrective measures to manage renal injury and thereby reduce its burden on health care.[5]
NS is most commonly used worldwide despite the strong association between its use and adverse biochemical outcomes in several surgeries. The emerging data support the use of isotonic BC in preference to NS in improving physiochemical outcomes. However, there is insufficient data on neurosurgical patients to recommend the change in practice. Thus, the present study was planned to compare these two crystalloids; plasmalyte and NS in patients who underwent craniotomies for TBI in terms of their effects on acid–base equilibrium, renal functions, and coagulation profile.
The primary objective was a comparison in terms of effects on acid–base equilibrium (pH, base excess [BE], and bicarbonate). The secondary objectives were a comparison regarding effects on renal functions (blood urea, serum creatinine, serum electrolytes, NGAL), and coagulation profile (prothrombin time, partial thromboplastin time, and international normalized ratio [INR]).
MethodsThe present prospective randomized double-blind study was carried out after obtaining approval from the institutional ethics committee and the study is also registered with clinicaltrial.gov (CTRI/2020/09/027624). The purpose and protocol of the study were explained and informed and witnessed consent for participation in the study was obtained from the kin or guardian of the patient.
Fifty patients of age 18–45 years of either sex, who underwent emergency craniotomy for TBI, were included in the study. Patients with associated injuries (long bone fracture and thoracic or abdominal injuries), hemodynamic instability, renal dysfunction, electrolyte imbalance, coagulation abnormalities, difficult airway, pregnancy and lactation, and comorbidities were excluded from the study.
Based on a study conducted by Dey et al. required sample size of a 5% level of significance and 95% power obtained was at least 21 patients in each group.[6] To compensate for a few dropouts, we enrolled 25 patients in each group.
Clinical history of the patient was taken which included any past significant history, presence of comorbidity, and timings of TBI. The general physical and systemic examination included neurological assessment, Glasgow Coma Score, pupil size, reactivity, respiration, and vitals parameters. The injury was graded as mild, moderate, or severe.
Findings of computed tomography (CT) scan (brain) and other investigations (hematological and biochemical) were noted.
The patients were randomized into two groups based on computer-generated randomization numbers. Group P (n = 25) received isotonic BC (plasmalyte) and Group N (n = 25) received NS intraoperatively and postoperatively till 24 h after surgery. Both the fluids were covered with opaque covers.
In the operating room, monitors for heart rate, noninvasive blood pressure, and pulse oximetry were attached. Intravenous access was obtained and a sample of blood was withdrawn and sent for a complete hemogram, blood urea, serum creatinine, serum electrolyte (sodium, potassium, and chloride), serum lactate, blood sugar, and coagulation profile (prothrombin time, partial thromboplastin time, and INR). Intravenous fluid was started as per group allocation. The left radial artery cannulation was done and arterial blood gas (ABG) analysis was done. Rapid sequence induction of anesthesia was done using fentanyl 2 μg/kg, thiopentone 5 mg/kg, and rocuronium 1 mg/kg. The airway was secured with an appropriate-size endotracheal tube if the patient was not tracheostomized.
Maintenance of anesthesia was done with oxygen (40%) and nitrous oxide (60%) in isoflurane (0.7–1 minimum anesthetic concentration [MAC]). Patients were ventilated with a ventilator from the Drager Primus workstation. Volume control mode was used with tidal volume 7 ml/kg, FiO2 = 0.4, Flow 3 L/min, I: E ratio 1:2, and frequency was adjusted to keep EtCO2 = 32–36 mmHg. Intraoperatively, fentanyl (1 mcg/kg/h) was given for analgesia and rocuronium (0.2 mg/kg/h) for neuromuscular relaxation as and when required. The surgery commenced and intraoperative fluids were administered as per the anesthesiologist's discretion to keep systolic blood pressure >110 mmHg. All the patients were given mannitol in a dose of 1 g/kg.
All the patients received 500 ml of colloid (6% HES) as a uniform protocol. Blood transfusion was done as per the American Society of Anesthesiologists (ASA) practices guidelines.[7]
One hour after the start of surgery, ABG analysis, electrolytes, and urea were repeated and thereafter at 12 h and 24 h.
If intraoperatively hypotension occurred which required more colloids, inotropes, or massive blood transfusion, patients were excluded from the analysis. Duration of surgery, amount of crystalloids, and blood administered were noted.
All patients were shifted to intensive care unit (ICU) care for 24 h and fluid continued as per group allocation at the rate of 2 ml/kg/hr. No nephrotoxic drug was administered. For pain relief, paracetamol infusion was given at 1 g six hourly. All the investigations done preoperatively were repeated. Any complications such as hypotension, bradycardia, or anaphylaxis were noted and managed accordingly. At 24 h venous sample was drawn, centrifuged, and stored at −80°C, and analysis for NGAL was done by ELISA method.
The entire data were entered into an MS Excel file and analyzed using appropriate statistical tests. The quantitative variables in both groups were expressed as mean ± standard deviation and compared using unpaired t-test between groups and paired t-test within each group at various follow-ups. The qualitative variables were expressed as frequencies/percentages and compared using the Chi-square test. For nonparametric data, Mann–Whitney U-test was performed. A P < 0.05 was considered statistically significant. Statistical Package for the Social sciences (SPSS) version 16.0 SPSS, IBM Corporation Company headquartered in (Armonk, New York, United States) was used for statistical analysis.
ResultsSeventy-five patients were assessed for recruitment. Twenty-five patients, not fulfilling the inclusion criteria, were excluded.
The two groups were comparable in terms of demographic profile as shown in [Table 1]. The intraoperative details are shown in [Table 2]; the two groups are comparable for the duration of surgery, intraoperative fluid and blood transfused, and blood loss. However, urine output is significantly higher in Group P (P < 0.05). The pH is lower in Group N (P < 0.05) at different time points after surgery. Similarly, more patients in Group N have pH <7.3 (P < 0.05); while the rest of the metabolic parameters were comparable in the two groups as shown in [Table 3]. Variations in serum electrolyte and renal profile in the two groups are shown in [Table 4]. The levels of serum NGAL (ng/ml) measured 24 h after surgery was 74.3 ± 14.9 versus 195.85 ± 0.17 in Groups P and N, respectively (P < 0.001). [Table 5] shows hemoglobin (Hb) and coagulation profile in two groups which are comparable. No patient had massive blood transfusions/inotropes.
DiscussionIn the present study, the metabolic profile was observed to be more favorable in patients who received plasmalyte. A statistically significant difference was observed between the two groups in terms of pH [Table 3]. Moreover, the number of patients who developed acidemia (defined as pH <7.35) was much higher in the NS group [Table 3]. The most probable explanation is the difference in the basic composition of the two fluids; the pH in NS is 5.6, whereas that of PL is 7.4. This leads to lower pH in the NS group. Moreover, NS infusion might result in hyperchloremic acidosis which is due to a reduction in strong ion difference by an excessive rise in plasma chloride as well as excessive renal bicarbonate elimination. Regarding pH, the results of the present study are in agreement with different studies.[8],[9],[10],[11],[12],[13],[14],[15] In a meta-analysis by Huang et al., patients in the NS group had significantly lower postoperative pH (MD: 0.05; 95% confidence interval [CI]: 0.04–0.06; P < 0.001; I2 = 82%) as compared to BC.[16]
In the present study, BE improved in both groups over time due to the resuscitation of the patients, but no statistically significant difference was observed between the two groups (P > 0.05) [Table 3]. Similar to the present study, Dey et al. did not find any significant difference between the two groups.[6] The result of the present study is in contrast to some studies regarding BE. Young et al. found that the mean BE was significantly improved with plasmalyte than with 0.9% NaCl from 0 to 24 h (7.5 ± 4.7 vs. 4.4 ± 3.9 mmol/L), respectively.[8] In a study done by Hassan et al., the NS group showed a significantly lower BE (−3.20 vs. −1.35, P = 0.049).[17] Patki et al. too observed that the difference in the base deficit was highly significant in the two groups at various time intervals.[10] In a meta-analysis done by Huang et al., patients in the NS group had significantly lower BE (MD: 2.04; 95% CI: 1.44–2.65; P < 0.001; I2 = 87%) as compared to BC.[16] The reasons for contradictory results in the present study could be due to different study populations, the nature of the surgery, or laboratory methods.
In the present study, it was observed that the values of HCO3 were higher in Group P as compared to Group N except 1 h after starting of surgery but these values from baseline to 24 h after surgery, were found to be statistically insignificant (P > 0.05) [Table 3]. Chowdhury et al. conducted a study to compare the effects of NS and plasmalyte 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers and observed that the bicarbonate values decreased over time in the NS group as compared to the baseline. However, values were statistically similar between the two groups.[18]
However, our results differ from most of the studies comparing these two types of fluids.[14],[17],[19] This could be a result of biochemical alterations in their study population due to underlying pathology. In a meta-analysis conducted by Huang et al., it was found that the serum bicarbonate level was significantly higher in the BC group postoperatively compared to the NS group (MD: 2.04; 95% CI: 1.23–2.85; P < 0.001; I2 = 85%).[16] However, in this analysis, the studies incorporated had used different types of BC.
In the present study, blood urea increase was more in Group N and this is signifying that in plasmalyte group there were less chances of AKI as compared to the NS group. Dey et al. observed the same results. Further, these authors also observed postoperative urea on the 5th day also and found a significant difference between the two groups (28.5 ± 16 mg/dl in the NS group vs. 24.82 ± 8.3 mg/dl in plasmalyte group).[6] Results regarding serum creatinine are in agreement with the study conducted by Dey et al. The difference from the present study is that these authors observed serum creatinine on the 5th postoperative day also and observed higher serum creatinine in the NS group 0.98 ± 0.2 mg/dl as compared to 0.74 ± 0.2 mg/dl (P < 0.001). Shaw et al. compared NS and BC in patients undergoing open abdominal surgeries. These authors observed a statistically significant increase (P = 0.001) in the incidence of renal failure mandating dialysis in patients who received NS.[20]
An increase in sodium levels from baseline was noted in Group N which was statistically significant at all time points [Table 4]. This is due to the difference in the composition of the two fluids. The findings of most of the studies are in consistence with our results.[8],[9],[12] In contrast to the present study, Hassan et al. compared two fluids (NS and BC) in patients admitted to the neurosurgical ICU following surgery for TBI and found no significant difference between the groups in terms of sodium levels.[17] However, they used a different fluid Sterofundin as BC. Regarding serum chloride levels, the results of the present study are in accordance with various studies.[6],[10],[14],[15],[17]
NGAL is considered to be one of the ideal and important biomarkers in the diagnosis of AKI. Normally, NGAL is not found in the urine or plasma of healthy individuals but it starts rising as early as within 6 h of clinical insult. In the present study, the value of NGAL in Group N was found to be 195.85 ± 60.17 ng/ml versus 74.53 ± 14.95 ng/ml in the P group (P < 0.001). Although we planned to assess NGAL levels in all the patients, the samples got spoilt while preservation and it was feasible in only 35 patients. Dey et al. also observed lesser value in patients who received BC (71.13 ± 28.7 ng/ml).[6] The difference from the present study is that these authors observed NGAL levels at 3 h after completion of surgery whereas, in the present study, it was observed at 24 h postoperatively. Funke et al. too observed significantly lower NGAL values in the BC group as compared to the NS group (39.4 ng/ml vs. 64.4 ng/ml).[21] The difference from the present study is that these authors used urinary NGAL level. Furthermore, clinically ill adults were included in their study.
TBI-induced coagulopathy manifests as disseminated intracranial hemorrhage, intracranial hematoma, and systemic bleeding. Fluids do play a crucial role in aggravating it by various mechanisms. There are limited studies evaluating the effects of various crystalloids on coagulation profiles. We used traditional markers (prothrombin time, partial thromboplastin time, and INR); the use of thromboelastogram and rotational thromboelastometry (ROTEM) would have been a better option but they were not available at our setup.
When the changes in PT were compared to the baseline, it was found to be statistically significant (P < 0.05) in Group P and insignificant in Group N (P > 0.05). However, we did not observe any statistically significant change in the values of activated partial thromboplastin time and INR in both the groups at baseline 12 h and 24 h postoperatively (P > 0.05). Our results corroborate with those by Song et al. who evaluated the effects of NS and PL on coagulation profile in patients undergoing lumbar spine surgery and concluded that clotting time, clot formation time, fibrin polymerization rate, and maximum clot firmness were statistically similar between the two groups.[11]
In the present study, baseline lactate levels were slightly higher in Group P but comparable to Group N [Table 3]. In the later course of time, lactate levels decreased due to proper resuscitation of the patients. During surgery, the levels were slightly higher in Group P most likely due to blood loss as this group received more amount of blood transfusion intraoperatively. During the rest of the time till 24 h of surgery, no difference in lactate levels was observed between the two groups.
Our findings are in accordance with different studies.[11],[17] However, Huang et al. in a meta-analysis reported higher lactate levels in the BC group as compared to the NS group.[16] However, they have included all the studies where different types of BC were used. The presence of lactate and acetate in the crystalloid may alter lactate levels but plasmalyte is devoid of these components resulting in absence of effects on lactate levels.
It is pertinent to check for h Hb levels in head injury patients since the anemia may impair cerebral oxygenation which, in turn, can aggravate secondary brain injury. Nevertheless, blood transfusion itself can lead to various complications. The threshold for blood transfusion is not defined, but at our center, we aim for Hb levels >9 g/dl. We observed that the baseline Hb levels were comparable in both groups. However, 24 h after surgery, a significant decline was noted in both groups. The levels were however comparable and so was the blood transfusion.
The use of nitrous oxide in neurosurgical patients continues to generate debate. Although it may increase cerebral blood flow, cerebral metabolic rate, and intracranial pressure, the magnitude is affected by the MAC of inhalational agents and the use of other drugs. The rise in intracranial pressure may be attenuated by prior administration of barbiturates, opioids, or hypocapnia. Further, it is considered neuroprotective as it is an N-methyl-D-aspartate antagonist.[22] If it is avoided, a large dosage of opioids might be required to take care of analgesia which will further make the patient hemodynamically unstable increasing the chances of secondary brain injury.[23]
Colloid was administered intraoperatively in both the groups in the present study so could not affect the study parameters. At our center, we use NS routinely in the postoperative period in these patients, although there are institution-to-institution variations.
There are some limitations of the study. The patients enrolled for the study were young, belonging to ASA I and II. It is difficult to comment if the same findings will be replicated in patients with comorbidities. The present study was restricted to 24 h after surgery; hence, long-term follow-up could not be done. The clinical significance of the study could not be derived. The patients could have received different fluids in the preoperative phase which was quite long for a few patients. The effect of those fluids on the results cannot be negated. Single-time renal biomarker (NGAL) levels were assessed, trends would have been more beneficial, but we could not perform it due to economic constraints.
ConclusionTo conclude, acid–base, electrolyte balance, and renal profile were better in patients receiving plasmalyte as compared to NS. Hence, it can be a wiser choice for fluid management in patients with TBI undergoing craniotomy.
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Conflicts of interest
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References
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